=5.7 cm, whereas increased
LVIDD value was detected in only one patient in the other two control groups.
There was a significant difference in terms of the presence of increased LVIDD
values between the MVP group and the control groups. Despite this enlargement in
the LV dimension, the LV ejection fractions were found similar in all groups.
Furthermore, it was found that the lengths of both anterior and posterior mitral
leaflets in MVP group were significantly higher than those in the control groups.
CONCLUSION: The LV diameters and volumes of patients with classic bileaflet MVP
were found to be increased even in the absence of significant MR. These results
need to be supported by large-scale clinical studies.
PMID- 22044563
TI - Insulin-like growth factor receptor expression is associated with aggressive
phenotypes and has therapeutic activity in biliary tract cancers.
AB - Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling is required for
carcinogenicity and progression of several cancers but the function of this
pathway and its utility as a therapeutic target have not been studied
comprehensively in biliary tract carcinomas (BTC). We investigated the
immunohistochemical expression of elements of the IGF axis, matrilysin,
overexpression of p53 and the methylation status of the IGFBP-3 promoter in 80
surgically resected BTC. We also assessed the effect of IGF-IR blockade on signal
transduction, proliferation and survival in three BTC cell lines using a new
tyrosine kinase inhibitor, BMS-536924, and dominant negative IGF-IR (IGF-IR/dn).
The effects of IGF-IR blockade was also studied in nude mouse xenograft models.
IGF-I was expressed in 60% and IGF-II in 50% of tumors. High expression was
associated with tumor size. IGF-IR was expressed in 69% of the cases and was
associated with advanced stage and matrilysin expression. Hypermethylation of the
IGFBP-3 promoter was detected in 41% of BTC and was inversely correlated with p53
expression. BMS-536924 blocked autophosphorylation of IGF-IR and both Akt and ERK
activation by both IGF-I and insulin. BMS-536924 suppressed proliferation and
tumorigenicity in vitro in a dose-dependent fashion. This inhibitor upregulated
chemotherapy-induced apoptosis in a dose-dependent fashion. Moreover, IGF-IR
blockade was effective against tumors in mice. IGF-IR might identify a subset of
BTC with a particularly aggressive phenotype and is a candidate therapeutic
target in this disease. BMS-536924 might have significant therapeutic utility.
PMID- 22044564
TI - Technical standardization of laparoscopic direct hernia repair in pediatric
patients.
AB - BACKGROUND: The aim of this article is to standardize the laparoscopic technique
to treat direct inguinal hernia in pediatric patients. PATIENTS AND METHODS: In
the last 3 years we treated laparoscopically 163 patients with a diagnosis of
inguinal hernia. In 7 patients we discovered laparoscopically a direct inguinal
hernia. This study is focused on the management of these 7 cases (4 girls and 3
boys; median age 4.6 years). They presented a right defect in 4 cases and a left
defect in 3 cases. Six of 7 patients had been already operated for an inguinal
hernia and presented a recurrence of the hernia. We used three trocars, 5-mm 0
degree optic, and two 3-mm instruments. In each case, after the resection of the
lipoma using the hook cautery, the defect was closed by means of separated
stitches. In every case we used the vesical ligament as an autologous patch to
reinforce the closure of the defect. RESULTS: The average operative time was 35
minutes. All the procedures were performed in a day-hospital setting. We had
neither conversions nor complications in our series. With a minimum follow-up of
1 year, we had no recurrence. CONCLUSIONS: Laparoscopic identification and repair
of direct inguinal hernia in children is a safe and effective procedure to adopt.
The key points of the technique are the resection of the lipoma, the closure of
the defect using separated, nonabsorbable sutures, and the use of the vesical
ligament to reinforce the suture. We believe that in case of recurrence of
inguinal hernias after inguinal approach, laparoscopy is the gold standard
technique to identify and treat the cause of the recurrence itself.
PMID- 22044565
TI - Endoscopic thyroidectomy: the development in a Chinese center.
AB - BACKGROUND: Endoscopic thyroidectomy (ET) precludes the long cervical incision of
the open procedure. Although endoscopy is an essential tool taught to almost
every surgeon, its effective use with regard to thyroidectomy requires
understanding its limitations pertaining to trauma and cancer, as well as an
understanding of the advantages and disadvantages of the different endoscopic
approaches. The development of an ET center in China is discussed here. METHODS:
Overall, 235 patients who had undergone attempted ET in Qilu Hospital of Shandong
University in China from August 2001 to September 2010 were evaluated. RESULTS:
Of the 11 men and 224 women on whom the procedure had been attempted, all but
seven successfully underwent ET, 145 (63.6%) via a modified anterior chest
approach, and 83 (36.4%) via a breast approach. Age ranged from 17 to 52 years,
with a mean of 34.5 years. Surgery was limited, in the case of masses, to lesions
smaller than 6 cm ultrasonographically. All patients were followed for at least 3
months. The 24 and 48 hours Visual Analog Scale postoperative measurements were
low. Complications included four cases of cutaneous emphysema, five seromas, four
episodes of anterior chest discomfort, three transient laryngeal nerve palsies,
and four episodes of hypocalcemia. The seven procedures that had been converted
to an open procedure comprised two patients discovered at frozen section to have
poorly differentiated thyroid carcinoma, two with tumors larger than 5 cm, and
three with thyroiditis. CONCLUSIONS: ET is readily learned, provided the surgeon
is competent at both laparoscopic technique and open thyroidectomy. Procedural
advantages of an endoscopic approach include superior cosmesis and decreased
invasiveness.
PMID- 22044566
TI - Ready or not--here we go into our future!!!
PMID- 22044567
TI - Fathers' perceptions of their roles during in-home training for children with
autism.
AB - PROBLEM: Currently, most research related to parents of children with autism has
focused on mothers, and little is known about the fathers' interaction with their
children. PURPOSE: The purpose of the qualitative study is to assist in more
fully describing and understanding fathers' perceptions of their roles,
relationships with their children with autism, and participation in an in-home
training intervention designed to enhance parent-child interactions as well as
child language and social interactions. METHODS: In depth semi-structured
interviews with 10 fathers were conducted at home, videotaped, transcribed, and
reviewed for common themes and significant statements FINDINGS: Five common
themes were discovered, fathers expressed their view of their roles, and fathers
reported the father-directed in-home intervention was effective in enhancing
father-child relationships. CONCLUSION: Communication between fathers and their
children appears to be the key to a successful relationship. Although verbal
communication deficit is a predominant feature of autism, these fathers noted
other ways of effective communicating including time spent playing or just being
with the child.
PMID- 22044568
TI - A relationship-based intervention to improve social connectedness in street
involved youth: a pilot study.
AB - PROBLEM: Street-involved youth experience a range of mental health problems with
elevated rates of psychiatric disorders compared with non-homeless youth. The
overall objective of this pilot study was to evaluate the impact of a
relationship-based intervention for homeless youth receiving services from
agencies in downtown Toronto. METHODS: The final sample included 15 homeless
youth who met the study inclusion criteria. The intervention and comparison
groups were compared at baseline and post-treatment on measures of mental health
symptoms, hopelessness, self-esteem, resilience, and social connectedness.
FINDINGS: Participants receiving the intervention demonstrated a significant
improvement in social connectedness, with a trend toward decreased hopelessness.
Those participants who did not receive the intervention did not demonstrate any
improvements in social connectedness and hopelessness. CONCLUSION: This
preliminary pilot study suggests that providing a relationship-based intervention
to street-involved youth may offer promise to strengthen social relationships and
to mitigate overwhelming hopelessness and despair.
PMID- 22044569
TI - Hopefulness among non-U.S.-born Latino youth and young adults.
AB - PROBLEM: U.S. Latino youths experience disproportionately high rates of health
and social problems. There is a need to identify protective factors for reducing
risky behaviors. Little is known about the protective nature of hope among
immigrant Latino adolescents. METHODS: This descriptive cross-sectional study
examined hope and expectations for the future in non-U.S.-born Latino adolescents
and young adults (n= 98) in urban and rural areas in the midwestern United
States. FINDINGS: Participants reported feeling hopeful about their future;
however, differences were detected among subgroups. CONCLUSION: Findings affirm
the potential of hope as a protective factor for immigrant Latino adolescents and
young adults. Nurses should be aware of hopefulness when implementing mental
health preventive interventions. Research is needed to identify effective
mechanisms for promoting and sustaining hope.
PMID- 22044570
TI - Consequences of intimate partner violence on child witnesses: a systematic review
of the literature.
AB - PROBLEM: Intimate partner violence (IPV) is a serious social problem that affects
all members of a household. Approximately 22% of violent crimes perpetrated
against women and 3% against men are related to IPV, and often children witness
these crimes. This paper addresses the evidence related to the short- and long
term consequences on the physical, psychosocial, and emotional status of child
witnesses. METHODS: A systemic review and analysis of the literature was
performed with 24 articles from 2000 to 2010 that were identified through
electronic search strategies. FINDINGS: Differences were found in the behaviors
of children who witness and do not witness IPV that have short- and long-term
consequences and affect relationships with same-sex peers, dating partners, and
future partners with a clear pattern of dose-response. CONCLUSIONS: Healthcare
providers can implement theoretically driven, gender and culturally appropriate
interventions for children with a history of IPV exposure with outcomes that
positively affect the lives of children.
PMID- 22044571
TI - Suicidal thought in the adolescent: exploring the relationship between known risk
factors and the presence of suicidal thought.
AB - PROBLEM: The purpose of this retrospective study was to explore the relationship
between recognized risk factors for suicidal thought and the presence or absence
of self-reported suicidal thought. METHODS: This study was conducted through the
secondary analysis of data obtained from a larger, prospective, cluster
randomized intervention study. A subset of 817 recruits between the ages of 17
and 19 was included in this study. FINDINGS: A personal history of mental
health/emotional problems and a decreased sense of belonging made unique
contributions to predicting the presence of suicidal thought. CONCLUSIONS: The
development of interventions to increase sense of belonging may be a key to
reducing suicidal thought during stressful events.
PMID- 22044572
TI - Young people's preferences for emotional well-being support in high school--a
focus group study.
AB - PROBLEM: Schools have been identified as a suitable setting for the delivery of
emotional well-being (EWB) support, but in the United Kingdom there is little
empirical evidence from young people that can inform the development of
appropriate school-based interventions. METHODS: Fifty-four students (11-16
years) from three U.K. high schools discussed the content, delivery, and
evaluation of acceptable, school-based, EWB support. Focus group methods were
matched to the school setting and sensitive topic. FINDINGS: Participants
identified emotional difficulties in school, home, and with peer relationships.
They said that some problems were too sensitive for them to seek help in school
setting. They valued confidentiality, support, and effective help that were
offered by people they experienced as friendly, trustworthy, and skilled.
Teachers and peer mentors were not thought to fit these criteria, although
trusted adults in mentor roles could meet their criteria. Participants recognized
that they could hide their emotions, so their EWB would be difficult to assess.
They described how the effect of emotional distress on their behavior is
idiosyncratic, and therefore their EWB should not be judged simply on their
behavior. CONCLUSION: The way in which EWB support is delivered in school is an
important aspect of the role of practitioners and educators attempting to provide
it. Because young people are sensitive to the personal qualities and skills of
people offering them help, programs to train school staff in emotional support
roles are important to ensure trust and an environment open to students seeking
assistance. Interventions for school-based EWB support need to consider
subjective well-being as well as behavioral change.
PMID- 22044574
TI - Genetic eye research in Tasmania: a historical overview.
AB - Although considerable recent work on hereditary eye diseases in Tasmanian
families has been published, much of this depended on a century of meticulous
pedigree collection by earlier clinical researchers. This article reviews some of
the historical papers and the importance they have played in gene discovery and
understanding of ophthalmic genetics. Tasmanian families have contributed to the
identification of genes for X-linked megalocornea, Leber's hereditary optic
neuropathy, retinitis pigmentosa, congenital cataract, ptosis, keratoconus,
glaucoma and myopia. The true value of the Tasmanian pedigrees will be realized
with the translation of genetic discoveries into early diagnosis and treatment
for these eye diseases.
PMID- 22044576
TI - Primary pulmonary hypertension, congenital heart defect, central nervous system
malformations, hypo- and aplastic toes: another case of Yunis-Varon syndrome or
report of a new entity.
AB - Here we describe a patient with a new malformation syndrome which shows
similarities with Yunis-Varon syndrome (YVS). Prenatal presentation included
polyhydramnios, increased nuchal translucency, and bilateral hydrothoraces
requiring pigtail insertion. Postnatal presentation revealed primary pulmonary
hypertension (PPH), persistent hydrothoraces, one atrial and two ventricular
septal defects, hypoplasia of the corpus callosum and cerebellar vermis, dilated
interhemispheric ventricles, severe developmental delay with general muscular
hypotonia, retinal anomalies, sparse scalp hair, sparse eyebrows and eyelashes,
hypo- and aplastic nails, low-set dysplastic ears, loose nuchal skin, hypo- and
aplastic distal phalanges of the toes as well as postnatal failure to thrive.
High resolution molecular karyotyping in the patient did not reveal any causative
chromosomal aberration. Since one patient with YVS and PPH has been previously
reported, we assume a similar pathogenic pathway. However, molecular confirmation
of the clinical diagnosis is not yet possible. It remains uncertain if the
presented syndrome can be classified as YVS with PPH or if it constitutes a new
YVS like entity.
PMID- 22044575
TI - Neutrophil extracellular traps promote deep vein thrombosis in mice.
AB - BACKGROUND: Upon activation, neutrophils can release nuclear material known as
neutrophil extracellular traps (NETs), which were initially described as a part
of antimicrobial defense. Extracellular chromatin was recently reported to be
prothrombotic in vitro and to accumulate in plasma and thrombi of baboons with
experimental deep vein thrombosis (DVT). OBJECTIVE: To explore the source and
role of extracellular chromatin in DVT. METHODS: We used an established murine
model of DVT induced by flow restriction (stenosis) in the inferior vena cava
(IVC). RESULTS: We demonstrate that the levels of extracellular DNA increase in
plasma after 6 h IVC stenosis, compared with sham-operated mice.
Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils
in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated
histone H3 (CitH3), an element of NETs' structure, was present only in the red
part of thrombi and was frequently associated with the Gr-1 antigen.
Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and
von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus
development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected
mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated
mixture of calf thymus histones increased plasma VWF and promoted DVT early after
stenosis application. CONCLUSIONS: Extracellular chromatin, likely originating
from neutrophils, is a structural part of a venous thrombus and both the DNA
scaffold and histones appear to contribute to the pathogenesis of DVT in mice.
NETs may provide new targets for DVT drug development.
PMID- 22044577
TI - General practitioners' views and experiences of counselling for physical activity
through the New Zealand Green Prescription program.
AB - BACKGROUND: Regular physical activity is beneficial in both the prevention and
management of chronic health conditions. A large proportion of adult New
Zealanders, however, are insufficiently active. To help increase population
levels of physical activity in New Zealand the Green Prescription, a primary care
physical activity scripting program, was developed. The primary aim of this study
was to identify why general practitioners (GPs) counsel for physical activity and
administer Green Prescriptions. A secondary aim was to examine GPs' views and
experiences of Green Prescription counselling for the management of depression.
METHODS: Individual face-to-face interviews were conducted with 15 GPs. All
interviews were audio-taped and transcribed. Data were analysed using an
inductive thematic approach. RESULTS: Several themes and sub-themes emerged from
the data. Notably, GPs counselled for physical activity and prescribed Green
Prescriptions for both primary preventive (e.g., weight control) and secondary
management (e.g., diabetes management) purposes. GPs reported the benefits of the
Green Prescription centred around two main themes: (i) a non-medication approach
to a healthier lifestyle and (ii) the support benefits of physical activity. Time
constraints within the consultation was the only main theme that emerged
regarding the barriers GPs perceived to Green Prescription use. Physical activity
in general, and physical activity prescribed through the Green Prescription, were
also viewed by GPs as beneficial for the management of depression. CONCLUSIONS:
The results of this study suggest that New Zealand GPs view the Green
Prescription program as beneficial for their patients with pre-existing
conditions and/or weight problems. While this is encouraging, the Green
Prescription may also be used to promote physical activity in currently healthy
but low-active and sedentary individuals. Such individuals are currently disease
free, but are at risk for future health-related problems because of their
inactive lifestyle. It is recommended that time constraints of the consultation
in regard to administering Green Prescriptions could be dealt with by delegating
the more time consuming tasks to the patient support counsellors that support the
Green Prescription program, and having practice nurses assist in the
administration of Green Prescriptions. Green Prescription counselling in
conjunction with antidepressant medication may be beneficial for the management
of depression and warrants further research.
PMID- 22044578
TI - Immunomodulatory properties of Xylaria nigripes in peritoneal macrophage cells of
Balb/c mice.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Wu Ling Shen, a folklore name for Xylaria
nigripes (XN), is a high value medicinal fungus used in traditional Chinese
medicine. AIM OF STUDY: The present study aimed to examine the immunomodulatory
properties of aqueous (XN-H) and ethanol (XN-E) XN extracts in lipopolysaccharide
(LPS)-induced peritoneal macrophage cells of Balb/c mice. MATERIALS AND METHODS:
After treating the macrophage cells with LPS (1 MUg/ml) and different XN
extracts, the immunomodulatory properties were determined by the responses of
inflammatory mediators, namely nitrite oxide (NO), prostaglandin E2 (PGE(2)) and
cytokine (IL-1beta, IL-6, TNF-alpha and IFN-gamma) production, iNOS, COX-2 and
IkappaB-alpha expression, and NF-kappaB activation. RESULTS: Results showed that
treatment of macrophages with 5-30 MUg/ml of XN-H or XN-E plus 1 MUg/ml LPS
exhibited no cytotoxic effect on cell viability. At these concentrations,
although both XN-H and XN-E showed a dose-dependent inhibitory effect on NO,
PGE(2), IL-1beta, IL-6, TNF-alpha and IFN-gamma production in LPS-stimulated
macrophages, a greater potency was noted in the XN-H treated group. RT-PCR assay
also showed that XN-H possessed a greater inhibition than XN-E on iNOS and COX-2
RNA expression. Furthermore, XN-H also showed a significant stronger suppression
than XN-E on the LPS-induced IkappaB-alpha phosphorylation and NF-kappaB
activation. XN-E showed a higher total flavonoid and phenol contents but a lower
beta-glucan content than XN-H. CONCLUSION: Taken together, these results conclude
that XN-H possesses a stronger anti-inflammatory activity than XN-E, and its
mechanism of action could be mediated by inhibiting iNOS and COX-2 expression via
the NF-kappaB signaling pathway, and these activities could be contributed by the
beta-glucan content.
PMID- 22044579
TI - Diagnosis and management of anaemia and iron deficiency in patients with
haematological malignancies or solid tumours in France in 2009-2010: the AnemOnHe
study.
AB - OBJECTIVE: To describe the management of anaemia in 2009-2010 in France in
patients with haematological malignancies (HM) or solid tumours (ST). METHODS:
Retrospective observational study in 57 centres, enrolling adult patients with HM
or ST treated for an episode of anaemia (duration of the episode >= 3 months
occurring in the last 12 months). RESULTS: 220 patients with ST (breast, 18%;
lung, 18%) and 56 with HM (lymphoma, 60%) were included (median age, 68 years;
female, 53%). Mean haemoglobin level at anaemia diagnosis was 9.3 +/- 1.4 g/dL
(<8 g/dL for 16%) and 9.8 +/- 1.1g/dL (<8 g/dL for 6%) in HM and ST patients,
respectively. At least one parameter of iron deficiency (ferritin, transferrin
saturation) was assessed in 26% of HM and 19% of ST patients. Treatment of
anaemia included erythropoiesis-stimulating agents (ESA) for 98% of HM and 89% of
ST patients. Iron was prescribed to 14% (oral, 12%; intravenous, 2%) of HM
patients and to 42% (oral, 17%; intravenous, 25%) of ST patients. The rates of
blood transfusions were high: 70% in HM and 46% in ST patients; transfusions
alone or administrated with ESA were more frequent in patients with Hb <8 g/dL.
CONCLUSION: Although recent guidelines recommend evaluating iron deficiency and
correcting anaemia by using intravenous iron, our study in cancer patients
evidenced that ESA and blood transfusions are still frequently used as the
treatment of anaemia in cancer patients. Iron deficiency is insufficiently
assessed (only one patient among five) and as a consequence iron deficiency is
most likely insufficiently treated.
PMID- 22044580
TI - A giant plexiform schwannoma of the brachial plexus: case report.
AB - We report the case of a patient who noticed muscle weakness in his left arm 5
years earlier. On examination, a biloculate mass was observed in the left
supraclavicular area, and Tinel's sign caused paresthesia in his left arm.
Magnetic resonance imaging showed a continuous, multinodular, plexiform tumor
from the left C5 to C7 nerve root along the course of the brachial plexus to the
left brachia. Tumor excision was attempted. The median and musculocutaneous
nerves were extremely enlarged by the tumor, which was approximately 40 cm in
length, and showed no response to electric stimulation. We resected a part of the
musculocutaneous nerve for biopsy and performed latissimus dorsi muscle
transposition in order to repair elbow flexion. Morphologically, the tumor
consisted of typical Antoni A areas, and immunohistochemistry revealed a Schwann
cell origin of the tumor cells moreover, there was no sign of axon
differentiation in the tumor. Therefore, the final diagnosis of plexiform
Schwannoma was confirmed.
PMID- 22044581
TI - A Bayesian model for gene family evolution.
AB - BACKGROUND: A birth and death process is frequently used for modeling the size of
a gene family that may vary along the branches of a phylogenetic tree. Under the
birth and death model, maximum likelihood methods have been developed to estimate
the birth and death rate and the sizes of ancient gene families (numbers of gene
copies at the internodes of the phylogenetic tree). This paper aims to provide a
Bayesian approach for estimating parameters in the birth and death model.
RESULTS: We develop a Bayesian approach for estimating the birth and death rate
and other parameters in the birth and death model. In addition, a Bayesian
hypothesis test is developed to identify the gene families that are unlikely
under the birth and death process. Simulation results suggest that the Bayesian
estimate is more accurate than the maximum likelihood estimate of the birth and
death rate. The Bayesian approach was applied to a real dataset of 3517 gene
families across genomes of five yeast species. The results indicate that the
Bayesian model assuming a constant birth and death rate among branches of the
phylogenetic tree cannot adequately explain the observed pattern of the sizes of
gene families across species. The yeast dataset was thus analyzed with a Bayesian
heterogeneous rate model that allows the birth and death rate to vary among the
branches of the tree. The unlikely gene families identified by the Bayesian
heterogeneous rate model are different from those given by the maximum likelihood
method. CONCLUSIONS: Compared to the maximum likelihood method, the Bayesian
approach can produce more accurate estimates of the parameters in the birth and
death model. In addition, the Bayesian hypothesis test is able to identify
unlikely gene families based on Bayesian posterior p-values. As a powerful
statistical technique, the Bayesian approach can effectively extract information
from gene family data and thereby provide useful information regarding the
evolutionary process of gene families across genomes.
PMID- 22044582
TI - Quantifying the environmental impact of As and Cr in stabilized/solidified
materials.
AB - The assessment of the quality of sediment from the Great Backi Canal (Serbia)
based on the pseudo-total As and Cr content according to the corresponding Dutch
standards and Canadian guidelines showed its severe contamination with these two
elements. Microwave assisted BCR sequential extraction procedure was employed to
assess their potential mobility and risk to the aquatic environment. Comparison
of the results of sequential extraction and different criteria for sediment
quality assessment has led to somewhat contradictory conclusions. While the
results of sequential extraction showed that Cr comes under the medium risk
category, As shows no risk to the environment, despite of its high pseudo-total
content. The contaminated sediment, irrespective of the different distribution of
As and Cr, was subjected to the same immobilization, stabilization/solidification
(S/S) treatment. Semi-dynamic leaching test was conducted for As and Cr
contaminated sediment in order to assess the long-term leaching behavior of these
elements. In order to simulate "worst case" leaching conditions, the test was
modified using acetic acid and humic acid solution as leachants instead of
deionized water. The effectiveness of S/S treatment was evaluated by determining
diffusion coefficients. Four different single-step leaching tests were applied to
evaluate the extraction potential of As and Cr. A diffusion-based model was used
to elucidate the controlling leaching mechanisms. The test results indicated that
all applied S/S treatments were effective in immobilizing As and Cr, irrespective
of their different availabilities in the untreated samples. In most treated
samples, the controlling leaching mechanism appeared to be diffusion, which
indicates that a slow leaching of As and Cr could be expected.
PMID- 22044583
TI - Influence of source distribution and geochemical composition of aerosols on
children exposure in the large polymetallic mining region of the Bolivian
Altiplano.
AB - The Bolivian Altiplano (Highlands) region is subject to intense mining, tailing
and smelting activities since centuries because of the presence of large and
unique polymetallic ore deposits (Ag, Au, Cu, Pb, Sn, Sb, Zn). A large scale
PM(10), PM(2.5) aerosol monitoring survey was conducted during the dry season in
one of the largest mining cities of this region (Oruro, 200,000 inhabitants).
Aerosol fractions, source distribution and transport were investigated for 23
elements at approximately 1 km(2) scale resolution, and compared to children
exposure data obtained within the same geographical space. As, Cd, Pb, Sb, W and
Zn in aerosols are present at relatively high concentrations when compared to
studies from other mining regions. Arsenic exceeds the European council PM(10)
guide value (6 ng/m(3)) for 90% of the samples, topping 200 ng/m(3). Ag, As, Cd,
Cu, Pb and Sb are present at significantly higher levels in the district located
in the vicinity of the smelter zone. At the city level, principal component
analysis combined with the mapping of factor scores allowed the identification
and deconvolution of four individual sources: i) a natural magmatic source (Co,
Cs, Fe, K, Mn, Na, Rb and U) originating from soil dust, resuspended by the
traffic activity; ii) a natural sedimentary source (Mg, Ca, Sr, Ba and Th)
resulting from the suspension of evaporative salt deposits located South; iii) an
anthropogenic source specifically enriched in mined elements (As, Cd, Cu, Pb, Sb
and Zn) mainly in the smelting district of the city; and iv) a Ni-Cr source
homogenously distributed between the different city districts. Enrichment factors
for As, Cd and Sb clearly show the impact of smelting activities, particularly in
the finest PM(2.5) fraction. Comparison to children's hair metal contents
collected in five schools from different districts shows a direct exposure to
smelting activity fingerprinted by a unique trace elements pattern (Ag, As, Cu,
Pb, Sb).
PMID- 22044584
TI - Continuous administration of poloxamer 188 reduces overload-induced muscular
atrophy in dysferlin-deficient SJL mice.
AB - Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy. We
demonstrated that poloxamer 188 (P188), a membrane sealant, is effective in
reducing the loss of muscle mass in SJL mice when administered using an osmotic
pump for 6 weeks. We did not observe significant changes over a 2-week
administration period, suggesting that longthier observation is necessary to
determine the effectiveness of P188. We also examined exercise endurance in P188
administered SJL mice using a rolling cage. Phosphorylated p38 was found to be
reduced in P188-administered SJL mice; additionally, using microarray analysis,
we found diminished expression of atrogin-1, an E3 ubiquitin ligase, as the
effector of muscular atrophy. Chronic infusion of P188 to dysferlin-deficient SJL
mice reduced muscular atrophy, and administering p38 and atrogin-1 in the
gastrocnemius muscle improved its motor function. These results provide a basis
for potential treatments for dysferlin-deficient skeletal muscle fibers.
PMID- 22044585
TI - Endurance exercise modifies the circadian clock in zebrafish (Danio rerio)
temperature independently.
AB - AIM: Several rodent and human studies revealed that physical exercise acts as a
non-photic zeitgeber for the circadian clock. The intrinsic entraining mechanism
is still unknown, although it was assumed that the exercise-mediated increase in
core temperature could be the underlying zeitgeber. As the homoeostatic control
of mammalian core temperature interferes strongly with the investigation of this
hypothesis, the present study used the poikilotherm zebrafish to answer this
question. METHODS: Gene transcription levels of the two circadian core clock
genes period1 and clock1 were quantified using real-time qPCR of whole animal
zebrafish larvae. RESULTS: Long-term endurance exercise of zebrafish larvae aged
9-15 days post-fertilization (dpf) or 21-32 dpf at a constant water temperature
of 25 degrees C caused significantly altered transcription levels of the
circadian genes period1 and clock1. Cosinor analysis of diurnal transcription
profiles obtained after 3 days of swim training revealed significant differences
regarding acrophase, mesor and amplitude of period1, resulting in a phase delay
of the gene oscillation. After termination of the exercise bout, at 15 dpf,
oscillation amplitudes of both circadian genes were significantly reduced.
CONCLUSION: The results showed that physical exercise is able to affect the
transcription of circadian genes in developing zebrafish larvae. Considering the
poikilothermy of zebrafish, an exercise-mediated change in body core temperature
could be excluded as the underlying intrinsic zeitgeber. However, the day-active
zebrafish arises as a useful model to address the synchronizing effect of
exercise on the circadian clock.
PMID- 22044586
TI - Effects of inclusion on the academic achievement and adaptive behaviour of
children with intellectual disabilities.
AB - BACKGROUND: While an extensive body of research has examined the outcomes of
inclusion for pupils with special needs, in particular learning disabilities, its
effects on the development of children with intellectual disabilities (ID) have
been less explored. As inclusive practices tend to be more common for this group
of children, it is important to acquire more knowledge on this issue. METHODS: A
comparative study with an experimental group of 34 children with ID fully
included in general education classrooms with support, and a control group of 34
comparable children in special schools has been conducted. The progress
accomplished by these two groups in their academic achievement and adaptive
behaviour has been compared over two school years. RESULTS: Included children
made slightly more progress in literacy skills than children attending special
schools. No differences were found between the progress of the two groups in
mathematics and adaptive behaviour. CONCLUSIONS: Inclusive education is an
appropriate educational option for primary pupils with ID who require extensive
support in school.
PMID- 22044588
TI - p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia.
AB - Inhibition of tumor suppressor p53 is cardioprotective against ischemic injury
and provides resistance to subsequent cardiac remodeling. We investigated p53
mediated expansion of ischemic damage with a focus on mitochondrial integrity in
association with autophagy and apoptosis. p53(-/-) heart showed that autophagic
flux was promoted under ischemia without a change in cardiac tissue ATP content.
Electron micrographs revealed that ischemic border zone in p53(-/-) mice had 5
fold greater numbers of autophagic vacuoles containing mitochondria, indicating
the occurrence of mitophagy, with an apparent reduction of abnormal mitochondria
compared with those in WT mice. Analysis of autophagic mediators acting
downstream of p53 revealed that TIGAR (TP53-induced glycolysis and apoptosis
regulator) was exclusively up-regulated in ischemic myocardium. TIGAR(-/-) mice
exhibited the promotion of mitophagy followed by decrease of abnormal
mitochondria and resistance to ischemic injury, consistent with the phenotype of
p53(-/-) mice. In p53(-/-) and TIGAR(-/-) ischemic myocardium, ROS production was
elevated and followed by Bnip3 activation which is an initiator of mitophagy.
Furthermore, the activation of Bnip3 and mitophagy due to p53/TIGAR inhibition
were reversed with antioxidant N-acetyl-cysteine, indicating that this adaptive
response requires ROS signal. Inhibition of mitophagy using chloroquine in p53(-/
) or TIGAR(-/-) mice exacerbated accumulation of damaged mitochondria to the
level of wild-type mice and attenuated cardioprotective action. These findings
indicate that p53/TIGAR-mediated inhibition of myocyte mitophagy is responsible
for impairment of mitochondrial integrity and subsequent apoptosis, the process
of which is closely involved in p53-mediated ventricular remodeling after
myocardial infarction.
PMID- 22044589
TI - Community health service capacity in China: a survey in three municipalities.
AB - RATIONALE: China is reforming its health care system. It aims to strengthen
primary health care through building community health facilities and assigning a
'gate-keeper' role to primary care providers. However, it remains unknown whether
community health facilities are able to fulfil such a mission. This study
evaluated the service capacity of a selected sample of community health
facilities and the competency of primary care practitioners employed by those
facilities. METHODS: Three municipalities from the east, middle and west of China
were purposely selected. A questionnaire was undertaken in 45 randomly selected
community health facilities in the three municipalities and 700 primary care
practitioners responded to the survey. The survey investigated the capacity of
the community health facilities in providing diagnostic services and the
competency of the primary care providers in handling common health problems.
RESULTS: The most common reasons for doctor-patient encounters were common cold
and chronic diseases. The capacity of the community health facilities in
providing diagnostic services was limited. Although the majority of respondents
believed that they could correctly identify common symptoms, many were unable to
perform some essential physical examinations. CONCLUSION: The community health
facilities are not able to fulfil their designated mission because of the limited
diagnostic capacity and poor competency of the primary care practitioners.
Priorities should be given to capacity building for the development of community
health services in the future.
PMID- 22044590
TI - Effects of rehydration nutrients on H2S metabolism and formation of volatile
sulfur compounds by the wine yeast VL3.
AB - In winemaking, nutrient supplementation is a common practice for optimising
fermentation and producing quality wine. Nutritionally suboptimal grape juices
are often enriched with nutrients in order to manipulate the production of yeast
aroma compounds. Nutrients are also added to active dry yeast (ADY) rehydration
media to enhance subsequent fermentation performance. In this study we
demonstrate that nutrient supplementation at rehydration also has a significant
effect on the formation of volatile sulfur compounds during wine fermentations.
The concentration of the 'fruity' aroma compounds, the polyfunctional thiols 3
mercaptohexan-1-ol (3MH) and 3-mercaptohexyl acetate (3MHA), was increased while
the concentration of the 'rotten egg' aroma compound, hydrogen sulfide (H2S), was
decreased. Nutrient supplementation of the rehydration media also changed the
kinetics of H2S production during fermentation by advancing onset of H2S
production. Microarray analysis revealed that this was not due to expression
changes within the sulfate assimilation pathway, which is known to be a major
contributor to H2S production. To gain insight into possible mechanisms
responsible for this effect, a component of the rehydration nutrient mix, the tri
peptide glutathione (GSH) was added at rehydration and studied for its subsequent
effects on H2S formation. GSH was found to be taken up during rehydration and to
act as a source for H2S during the following fermentation. These findings
represent a potential approach for managing sulfur aroma production through the
use of rehydration nutrients.
PMID- 22044591
TI - Which patients are at the highest risk of dying from competing causes <= 10 years
after radical prostatectomy?
AB - Study Type - Outcomes (cohort). Level of Evidence 2b. What's known on the
subject? and What does the study add? Several comorbidity classifications have
been investigated for their suitability to assist treatment decision-making in
men with early prostate cancer. In unselected patients, some serious
comorbidities have been shown to be associated with a 10-year competing mortality
rate clearly superseding the 50% level. The present study shows that it is hardly
possible to discern meaningful subsets of patients with a 10-year risk of
competing mortality of >50% by using comorbidity classifications. This finding
suggests that the selecting clinicians did well in estimating the medium-term
survival probability in men referred for radical prostatectomy. OBJECTIVE: * To
identify subsets of patients who are most likely to die from competing causes <=
10 years after radical prostatectomy (RP). PATIENTS AND METHODS: * In all, 2205
consecutive patients who underwent RP for clinically localized prostate cancer
between 1992 and 2005 were studied. The 10-year cumulative competing mortality
rates were determined in several worst-case scenarios formed by using comorbidity
classifications and combinations of them. RESULTS: * In this sample of men
selected for RP, even those with the most severe comorbidity level had a
competing mortality risk of <50% <= 10 years after RP. * Depending on the
comorbidity classification used, the 10-year cumulative competing mortality rates
differed between 16 and 39% in the whole sample and between 18 and 48% in men
aged >= 65 years. CONCLUSION: * Clinicians do well in estimating the further life
span in candidates for RP. Comorbidity classifications may assist treatment
choice in this population but are not able to discern meaningful subsets to be
excluded from curative treatment because of a life expectancy falling below a
limit of 10 years.
PMID- 22044592
TI - Cor triatriatum dextro iatrogenica: an unusual complication of atrial septal
defect closure device.
AB - We present a case of a rare complication of atrial septal defect (ASD) device
closure causing cor triatriatum dextro iatrogenica. A 29-year-old female
presented with sudden onset dysarthria and ataxia and was found to have basilar
and thalamic infarcts. Further evaluation using transthoracic echocardiography
revealed an ASD which was repaired using the Gore HELEX septal occluder.
Transesophageal echocardiography done after 2 months of ASD closure revealed an
interesting finding termed cor triatriatum dextro iatrogenica. We briefly
describe the case and discuss the relevant literature.
PMID- 22044593
TI - Central nervous system event in patients with diffuse large B-cell lymphoma in
the rituximab era.
AB - Central nervous system (CNS) events, including CNS relapse and progression to
CNS, are known to be serious complications in the clinical course of patients
with lymphoma. This study aimed to evaluate the risk of CNS events in patients
with diffuse large B-cell lymphoma in the rituximab era. We performed a
retrospective survey of Japanese patients diagnosed with diffuse large B-cell
lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between
September 2003 and December 2006. Patients who had received any prophylactic CNS
treatment were excluded. Clinical data from 1221 patients were collected from 47
institutions. The median age of patients was 64 years (range, 15-91 years). We
noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events
was 8.4%. Patients with a CNS event demonstrated significantly worse overall
survival (P < 0.001). The 2-year overall survival rate after a CNS event was
27.1%. In a multivariate analysis, involvement of breast (relative risk [RR]
10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent
risk factors for CNS events. We conclude that patients with these risk factors,
in addition to patients with testicular involvement in whom CNS prophylaxis has
been already justified, are at high risk for CNS events in the rituximab era. The
efficacy and manner of CNS prophylaxis in patients for each involvement site
should be evaluated further.
PMID- 22044594
TI - Extrapyramidal adverse drug reactions associated with trimetazidine: a series of
21 cases.
AB - Over the last few years, a number of cases of extrapyramidal disorders associated
with trimetazidine (TMZ) use has been reported. Here, we report on a series of 21
cases. All but one of the patients (mean age 74) had been taking TMZ for several
years. The indication for prescription of TMZ could not be identified in seven
cases. The TMZ-associated adverse drug reactions were typical parkinsonism
(akinesia and/or rigidity and/or rest tremor) in 17 cases, gait disorders in
three cases (one with orthostatic tremor), and restless leg syndrome in one case.
Discontinuation of TMZ led to complete disappearance of the symptoms in 16 cases
and a significant reduction in the five other patients. TMZ has the same
piperazine core as the dopamine antagonists flunarizine and cinnarizine (both of
which have been reported to induce extrapyramidal symptoms). Hence, striatal D2
receptor blockade could result in the onset or the worsening of extrapyramidal
disorders. Even though this adverse drug reaction is now listed in TMZ's Summary
of Product Characteristics (because of the initial reports), the risk remains
poorly known by clinicians. There is a need to raise awareness of this phenomenon
and to reassess TMZ 's risk-benefit ration, especially in the elderly.
PMID- 22044595
TI - Use of CNS medications and cognitive decline in the aged: a longitudinal
population-based study.
AB - BACKGROUND: Previous studies have found associations between the use of central
nervous system medication and the risk of cognitive decline in the aged. Our aim
was to assess whether the use of a single central nervous system (CNS) medication
and, on the other hand, the combined use of multiple CNS medications over time
are related to the risk of cognitive decline in an older (>= 65 yrs) population
that is cognitively intact at baseline. METHODS: We conducted a longitudinal
population-based study of cognitively intact older adults. The participants were
65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of
24 points or higher. The study included a 7.6-year follow-up. The use of
benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants
(ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was
determined at baseline and after a 7.6-years of the follow-up period. Cognitive
functioning was used as an outcome variable measured with MMSE at baseline and at
the mean follow-up of 7.6 years. Control variables were adjusted with analyses of
covariance. RESULTS: After adjusting for control variables, the use of Ops and
the concomitant use of Ops and BZDs as well as the use of Ops and any CNS
medication were associated with cognitive decline. The use of AChs was associated
with decline in cognitive functioning only in men. CONCLUSIONS: Of all the CNS
medications analyzed in this study, the use of Ops may have the greatest effect
on cognitive functioning in the ageing population. Due to small sample sizes
these findings cannot be generalized to the unselected ageing population. More
studies are needed concerning the long-term use of CNS medications, especially
their concomitant use, and their potential cognitive effects.
PMID- 22044596
TI - Bioengineering of coagulation factor VIII for efficient expression through
elimination of a dispensable disulfide loop.
AB - BACKGROUND: Heterologous expression of factor VIII (FVIII) is about two to three
orders of magnitude lower than similarly sized proteins. Bioengineering
strategies aimed at different structural and biochemical attributes of FVIII have
been successful in enhancing its expression levels. OBJECTIVE: Disulfide bonds
are vital to the proper folding, secretion and stability of most secretory
proteins. In an effort to explore additional targeted bioengineering approaches,
the role of disulfide bonds in FVIII secretion and function was probed in this
study. METHODS AND RESULTS: Single and paired cysteine mutants were generated by
substituting with serine or glycine residues and analyzed by transient
transfection into COS-1 and CHO cells. Seven of the eight disulfide bonds in
FVIII were found to be indispensable for proper secretion and function. However,
elimination of the disulfide bond formed by C1899 and C1903 within the conserved
A3 domain improved the secretion of FVIII. The addition of the C1899G/C1903G
mutations to a previously described FVIII variant, 226/N6, with high secretion
efficiency increased its secretion by 2.2-fold. Finally, the addition of the A1
domain mutation, F309S, in conjunction with the disulfide mutation had an
additive effect, resulting in a net improvement in secretion of between 35 and 45
fold higher than wild-type FVIII in CHO cells. CONCLUSION: Such combined targeted
bioengineering strategies may facilitate more efficient production of recombinant
FVIII and contribute toward low-cost factor replacement therapy for hemophilia A.
PMID- 22044597
TI - H. pylori exploits and manipulates innate and adaptive immune cell signaling
pathways to establish persistent infection.
AB - Persistent infection with the gastric bacterial pathogen Helicobacter pylori
causes gastritis and predisposes carriers to a high gastric cancer risk, but has
also been linked to protection from allergic, chronic inflammatory and autoimmune
diseases. In the course of tens of thousands of years of co-existence with its
human host, H. pylori has evolved elaborate adaptations that allow it to persist
in the hostile environment of the stomach in the face of a vigorous innate and
adaptive immune response. For this review, we have identified several key immune
cell types and signaling pathways that appear to be preferentially targeted by
the bacteria to establish and maintain persistent infection. We explore the
mechanisms that allow the bacteria to avoid detection by innate immune cells via
their pattern recognition receptors, to escape T-cell mediated adaptive immunity,
and to reprogram the immune system towards tolerance rather than immunity. The
implications of the immunomodulatory properties of the bacteria for the
prevention of allergic and auto-immune diseases in chronically infected
individuals are also discussed.
PMID- 22044598
TI - The Foxconn suicides and their media prominence: is the Werther Effect applicable
in China?
AB - BACKGROUND: Media reporting of suicide and its relationship with actual suicide
has rarely been investigated in Mainland China. The "Foxconn suicides" is a
description referring to a string of suicides/attempts during 2010, all of which
were related to a giant electrical manufacturing company, Foxconn. This study
aimed to examine the clustering and copycat effects of the Foxconn suicides, and
to investigate temporal patterns in how they were reported by the media in
Mainland China, Hong Kong (HK), and Taiwan (TW). METHODS: Relevant articles were
collected from representative newspapers published in three big cities in
Mainland China (Beijing (BJ), Shenzhen (SZ), and Guangzhou (GZ)), HK, and TW,
together with searching intensity data on the topic conducted using the Baidu
search engine in Mainland China. The temporal clustering effects of the Foxconn
suicides and their media prominence were assessed using the Kolmogorov-Smirnov
test. The media reports of the Foxconn suicides' temporal patterns were explored
using a nonparametric curve estimation method (that is, the local linear method).
The potential mutual interactions between the Foxconn suicides and their media
prominence were also examined, using logistic and Poisson regression methods.
RESULTS: The results support a temporal clustering effect for the Foxconn
suicides. The BJ-based newspapers' reporting and the occurrence of a Foxconn
suicide/attempt are each found to be associated with an elevated chance of a
further Foxconn suicide 3 days later. The occurrence of a Foxconn suicide also
immediately influenced the intensity of both Baidu searching and newspaper
reporting. Regional diversity in suicide reporting tempo-patterns within Mainland
China, and similarities between HK and TW, are also demonstrated. CONCLUSIONS:
The Foxconn suicides were temporally clustered. Their occurrences were influenced
by the reporting of BJ-based newspapers, and contagion within the company itself.
Further suicide research and prevention work in China should consider its special
media environment.
PMID- 22044599
TI - Visceral and mucosal involvement in neonatal haemangiomatosis.
AB - BACKGROUND: Two types of neonatal haemangiomatosis (NH) are distinguished:
diffuse which is associated with a high rate of mortality linked to
mucosal/visceral involvement, and benign. OBJECTIVES: First, this study aimed to
examine the frequency of mucosal and visceral (especially hepatic) involvement in
NH, according to skin extension, and second, it aimed to examine clinical,
pathological (with glucose transporter 1 (GLUT-1) immunostaining), and imaging
features of NH, including follow-up data. METHODS: This was a descriptive
retrospective study carried out in the University Hospital Center of Tours,
France. RESULTS: The study included 19 patients with cutaneous NH (number of skin
haemangiomas ranging from 5 to >100). Mucosal involvement was observed in 32% of
all cases (100% and 19% in diffuse and other cutaneous cases respectively) and
hepatic involvement in 42% (67% and 38% respectively). The number of hepatic
haemangiomas ranged from 1 to >10. Half of the hepatic haemangiomas cases
exhibited increased hepatic arterial blood flow. CONCLUSIONS: Mucosal and hepatic
involvement was frequent in cases with a high number of cutaneous haemangiomas
(>100), but only frequency of mucosal involvement was statistically significant
(P = 0.021).
PMID- 22044600
TI - MALDI-TOF MS Andromas strategy for the routine identification of bacteria,
mycobacteria, yeasts, Aspergillus spp. and positive blood cultures.
AB - All organisms usually isolated in our laboratory are now routinely identified by
matrix-assisted laser desorption ionization-time of flight mass spectrometry
(MALDI-TOF MS) using the Andromas software. The aim of this study was to describe
the use of this strategy in a routine clinical microbiology laboratory. The
microorganisms identified included bacteria, mycobacteria, yeasts and Aspergillus
spp. isolated on solid media or extracted directly from blood cultures. MALDI-TOF
MS was performed on 2665 bacteria isolated on solid media, corresponding to all
bacteria isolated during this period except Escherichia coli grown on chromogenic
media. All acquisitions were performed without extraction. After a single
acquisition, 93.1% of bacteria grown on solid media were correctly identified.
When the first acquisition was not contributory, a second acquisition was
performed either the same day or the next day. After two acquisitions, the rate
of bacteria identified increased to 99.2%. The failures reported on 21 strains
were due to an unknown profile attributed to new species (9) or an insufficient
quality of the spectrum (12). MALDI-TOF MS has been applied to 162 positive blood
cultures. The identification rate was 91.4%. All mycobacteria isolated during
this period (22) were correctly identified by MALDI-TOF MS without any
extraction. For 96.3% and 92.2% of yeasts and Aspergillus spp., respectively, the
identification was obtained with a single acquisition. After a second
acquisition, the overall identification rate was 98.8% for yeasts (160/162) and
98.4% (63/64) for Aspergillus spp. In conclusion, the MALDI-TOF MS strategy used
in this work allows a rapid and efficient identification of all microorganisms
isolated routinely.
PMID- 22044601
TI - Fatty acid profiling and molecular characterization of some freshwater microalgae
from India with potential for biodiesel production.
AB - We determined the fatty acid compositions of six species of freshwater microalgae
belonging to the Chlorophyta, which were isolated from freshwater bodies in
Assam, India. All six microalgae -Desmodesmus sp. DRLMA7, Desmodesmus elegans
DRLMA13, Scenedesmus sp. DRLMA5, Scenedesmus sp. DRLMA9 Chlorella sp. DRLMA3 and
Chlorococcum macrostigmatum DRLMA12-showed similar fatty acid profiles 16:0,
16:4, 18:1, 18:2, and 18:3 as major components. We also compared fatty acid
compositions during the late exponential and stationary growth phases of D.
elegans DRLMA13 and Scenedesmus sp. DRLMA9 in BG11 medium. We observed enhanced
percentages of total saturated and monounsaturated fatty acids with a concomitant
decrease in polyunsaturated fatty acid content upon the prolonged cultivation of
both microalgae. Distinct morphological features of microalgal isolates were
determined by scanning electron microscopic (SEM) studies. An ornamented cell
wall was found in D. elegans DRLMA13, which is characteristic of small spineless
species of Desmodesmus. The isolated microalgae were further distinguished
through analysis of internal transcribed spacer 2 (ITS2) secondary structures and
compensatory base changes (CBCs). Analysis of CBCs showed the relatedness of
Chlorella sp. DRLMA3 with other Chlorella-like organisms, but it does not belong
to the clade comprising Chlorella sensu stricto, which includes Chlorella
vulgaris. The CBC count between Scenedesmus sp. DRLMA9 and other species of
Scenedesmus provides evidence that this isolate represents a new species.
PMID- 22044602
TI - Generalized shrinkage F-like statistics for testing an interaction term in gene
expression analysis in the presence of heteroscedasticity.
AB - BACKGROUND: Many analyses of gene expression data involve hypothesis tests of an
interaction term between two fixed effects, typically tested using a residual
variance. In expression studies, the issue of variance heteroscedasticity has
received much attention, and previous work has focused on either between-gene or
within-gene heteroscedasticity. However, in a single experiment,
heteroscedasticity may exist both within and between genes. Here we develop
flexible shrinkage error estimators considering both between-gene and within-gene
heteroscedasticity and use them to construct F-like test statistics for testing
interactions, with cutoff values obtained by permutation. These permutation tests
are complicated, and several permutation tests are investigated here. RESULTS:
Our proposed test statistics are compared with other existing shrinkage-type test
statistics through extensive simulation studies and a real data example. The
results show that the choice of permutation procedures has dramatically more
influence on detection power than the choice of F or F-like test statistics. When
both types of gene heteroscedasticity exist, our proposed test statistics can
control preselected type-I errors and are more powerful. Raw data permutation is
not valid in this setting. Whether unrestricted or restricted residual
permutation should be used depends on the specific type of test statistic.
CONCLUSIONS: The F-like test statistic that uses the proposed flexible shrinkage
error estimator considering both types of gene heteroscedasticity and
unrestricted residual permutation can provide a statistically valid and powerful
test. Therefore, we recommended that it should always applied in the analysis of
real gene expression data analysis to test an interaction term.
PMID- 22044603
TI - Effect of chloroethene concentrations and granular activated carbon on reductive
dechlorination rates and growth of Dehalococcoides spp.
AB - This study focused on the investigation of (i) the tetrachloroethene (PCE)
toxicity threshold of a reductively dechlorinating mixed culture containing
Dehalococcoides spp., (ii) the adsorption of PCE on different types of granular
activated carbon (GAC), and (iii) the bioavailability and reductive
dechlorination in the presence of GAC. The abundance of Dehalococcoides spp.
detected by quantitative real-time polymerase chain reaction (qPCR) was found to
increase by 2-4 orders of magnitude during degradation of PCE. No degradation
occurred at dissolved concentrations beyond 420 MUM (70 mg/L). Different
adsorption isotherms were determined for thermally and chemically activated
carbons. The addition of GAC to biological assays reduced the dissolved PCE
concentration below the toxicity threshold. The combination of microbial
reductive dechlorination with GAC adsorption proved to be a promising method for
remediation of groundwater contaminated by high concentrations of chloroethenes.
PMID- 22044604
TI - Watching the fetal brain at 'rest'.
AB - Functional magnetic resonance imaging (fMRI) has allowed insights into the
spatiotemporal distribution of human brain networks. According to the
neurophysiological property of the fetal brain to generate spontaneous activity,
we aimed to determine the feasibility of investigating the maturation of
intrinsic networks, beginning at gestational week 20 in healthy human fetuses by
combining resting-state fMRI and an analytical approach, independent component
analysis (ICA). In this study, functional images of 16 fetuses with
morphologically normal brain development, from 20 to 36 gestational weeks of age,
were acquired on a 1.5T unit (Philips Medical Systems, Best, The Netherlands)
using single-shot, gradient-recalled echo-planar imaging. After preprocessing
(motion correction, brain extraction), images were analyzed using single-subject
ICA. We visualized a bilateral occipital network and medial and lateral
prefrontal activity pattern that involved the future Brodmann areas 9-11.
Furthermore, there was one either predominantly right (3/7 cases) or left (4/7
cases) hemispheric lateralized network that involved the superior temporal
cortical regions (Brodmann areas 22 and 39). Frequency oscillations were in the
range of 0.01-0.06Hz for all networks. This study shows that resting-state
networks (RSNs) are shaped and are detectable in utero. Further investigations of
resting-state measurements in the fetus may therefore allow developmental brain
activity monitoring and may provide insights into early brain function.
PMID- 22044605
TI - Clinical/pathologic features and patient outcome in early onset endometrial
carcinoma: a population based analysis and an institutional perspective from the
Detroit metropolitan area, Michigan.
AB - OBJECTIVE: Analyze tumor characteristics and outcomes in patients with
endometrial carcinoma (EC)<40 years of age and compare them to the
characteristics of patients >= 40 years of age. METHODS: 10,700 patients (305
patients <40 years of age) diagnosed between 1988 and 2007 with EC from the
Metropolitan Detroit Cancer Surveillance System (MDCSS), and 884 patients (42
patients <40 years of age) diagnosed between 1996 and 2008 with EC from our
institutional database were identified. Differences in clinical and demographic
variables by age (<40 vs. >= 40) were assessed for statistical significance by
chi-square tests. Cox proportional hazards models were used to calculate adjusted
hazard ratios (HR) and their 95% confidence intervals (95% CI) to assess the risk
of death from all causes. RESULTS: MDCSS based analysis: Patients<40 were more
likely to present with low grade tumors (p<0.0001) and endometroid histology
(p=0.0004) but less likely to undergo surgery (p=0.0007) or radiotherapy
(p=0.0007). A multivariate analysis confirmed the significance of age, grade, and
stage in all patients, and that of histologic type, surgery, and race in patients
>= 40 as independent prognostic factors for overall survival. Institution based
analysis: Patients<40 had a higher proportion of patients with BM I >= 30
(p=0.04), and presented with a higher frequency of well differentiated (p=0.04)
endometrioid tumors (p=0.004) that are less prone to have deep myometrial
invasion (p=0.008). CONCLUSION: This study supports the hypothesis of a disease
that is biologically and genetically heterogeneous among women of different ages
and ethnicities.
PMID- 22044606
TI - A phase II trial of pemetrexed in combination with carboplatin in patients with
recurrent ovarian or primary peritoneal cancer.
AB - OBJECTIVE: Carboplatin-based combinations are commonly used in platinum-sensitive
ovarian cancer (PSOC). Pemetrexed in combination with carboplatin has been shown
to be feasible in a phase I study in PSOC. The primary objective of this
subsequent phase II study was to determine the overall response rate (ORR;
defined by Response Evaluation Criteria in Solid Tumors) of this combination in
patients with recurrent PSOC. Secondary objectives included progression-free
survival (PFS), overall survival (OS), and toxicity. METHODS: Patients with PSOC
(defined by recurrence >= 6 months after completion of up to two lines of prior
platinum-based therapy), measurable disease, Eastern Cooperative Oncology Group
performance status of 0 to 2, and adequate organ function were eligible.
Pemetrexed 500 mg/m(2) was administered as a 10-minute infusion followed by
carboplatin AUC 6 as a 30-minute infusion on day 1 of a 21-day cycle. RESULTS:
Sixty-six patients were treated. Of the 61 patients evaluable for response, there
were 20 responders (one complete response and 19 partial responses), for an ORR
of 32.8% (95% CI: 21.3%, 46.0%). For the intent-to-treat population (all 66
patients), the median PFS was 9.4 months (95% CI: 8.3, 11.1), with 22.7%
censoring. Median OS was not reached due to the high censoring rate. There was
one drug-related death (multi-organ failure). The most common drug-related grade
3/4 toxicities were neutropenia (39.4%), thrombocytopenia (24.2%), carboplatin
hypersensitivity (9.1%), nausea (6.1%), and vomiting (6.1%). CONCLUSIONS:
Carboplatin AUC 6 and pemetrexed 500 mg/m(2) has a low incidence of serious
toxicities. Defining the platinum-based combination with the best therapeutic
index would require a prospective phase III study.
PMID- 22044607
TI - Xeroderma pigmentosum.
AB - Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight,
resulting in sunburn, pigment changes in the skin and a greatly elevated
incidence of skin cancers. It is a rare autosomal recessive disorder and has been
found in all continents and racial groups. Estimated incidences vary from 1 in
20, 000 in Japan to 1 in 250, 000 in the USA, and approximately 2.3 per million
live births in Western Europe.The first features are either extreme sensitivity
to sunlight, triggering severe sunburn, or, in patients who do not show this sun
sensitivity, abnormal lentiginosis (freckle-like pigmentation due to increased
numbers of melanocytes) on sun-exposed areas. This is followed by areas of
increased or decreased pigmentation, skin aging and multiple skin cancers, if the
individuals are not protected from sunlight. A minority of patients show
progressive neurological abnormalities. There are eight XP complementation
groups, corresponding to eight genes, which, if defective, can result in XP. The
products of these genes are involved in the repair of ultraviolet (UV)-induced
damage in DNA. Seven of the gene products (XPA through G) are required to remove
UV damage from the DNA. The eighth (XPV or DNA polymerase eta) is required to
replicate DNA containing unrepaired damage. There is wide variability in clinical
features both between and within XP groups. Diagnosis is made clinically by the
presence, from birth, of an acute and prolonged sunburn response at all exposed
sites, unusually early lentiginosis in sun-exposed areas or onset of skin cancers
at a young age. The clinical diagnosis is confirmed by cellular tests for
defective DNA repair. These features distinguish XP from other photodermatoses
such as solar urticaria and polymorphic light eruption, Cockayne Syndrome (no
pigmentation changes, different repair defect) and other lentiginoses such as
Peutz-Jeghers syndrome, Leopard syndrome and Carney complex (pigmentation not sun
associated), which are inherited in an autosomal dominant fashion. Antenatal
diagnosis can be performed by measuring DNA repair or by mutation analysis in CVS
cells or in amniocytes. Although there is no cure for XP, the skin effects can be
minimised by rigorous protection from sunlight and early removal of pre-cancerous
lesions. In the absence of neurological problems and with lifetime protection
against sunlight, the prognosis is good. In patients with neurological problems,
these are progressive, leading to disabilities and a shortened lifespan.
PMID- 22044608
TI - Mirror images: fish versus terrestrial animals.
PMID- 22044610
TI - D-dimer levels as a prognostic factor for determining oncological outcomes in
musculoskeletal sarcoma.
AB - BACKGROUND: Plasma d-dimer levels have been associated with the status of tumor
progression or oncological outcomes in cancer. Although there are many evidences
suggesting the involvement of procoagulant trend in musculoskeletal sarcoma, no
clinical data on d-dimer levels and oncological outcome of musculoskeletal
sarcoma has been reported. METHODS: In this study, we included a total of 85
patients who were diagnosed with musculoskeletal sarcoma and treated at our
institute. Plasma d-dimer levels were determined before performing any clinical
intervention, including open biopsy, chemotherapy, radiotherapy or tumor
resection. We evaluated the effect of d-dimer levels and other
clinicopathological factors on oncological outcomes of patients. RESULTS:
Upregulation of plasma d-dimer levels proved to be an independent risk factor for
metastasis and lethal outcome of patients with musculoskeletal sarcoma.
CONCLUSIONS: Upregulation of plasma d-dimer levels were indicated poor
oncological outcome in metastasis and total survival rate of musculoskeletal
sarcoma patients. Hence d-dimer levels may be a helpful marker for evaluating the
tumor progression status and prognosis of musculoskeletal sarcoma.
PMID- 22044609
TI - Motivational brief intervention for the prevention of sexually transmitted
infections in travelers: a randomized controlled trial.
AB - BACKGROUND: Sexually transmitted infections (STIs) are among the frequent risks
encountered by travelers. Efficient interventions are needed to improve the
understanding of the risks of STIs. We investigated the potential benefits of a
motivational brief intervention (BI) and the provision of condoms on the
engagement in unprotected casual sex. METHODS: 3-arm randomized controlled trial
performed among single travelers aged 18-44 years visiting a travel clinic in
Switzerland. The main outcomes were the prevalence of casual unprotected sexual
intercourse and their predictors. RESULTS: 5148 eligible travelers were seen from
2006 to 2008. 1681 agreed to participate and 1115 subjects (66%) completed the
study. 184/1115 (17%) had a casual sexual relationship abroad and overall 46/1115
(4.1%) had inconsistently protected sexual relations. Women (adjusted OR 2.7
[95%CI 1.4-5.6]) and travelers with a history of past STI (adjusted OR 2.8 [95%CI
1.1-7.4]) had more frequent casual sexual relationships without consistent
protection. Regarding the effect of our intervention, the prevalence of subjects
using condoms inconsistently was 28% (95%CI16-40) in the motivational BI group,
24% (95%CI10-37) in the condoms group and 24% (95%CI14-33) in the control group
(p = 0.7). CONCLUSION: This study showed that a motivational brief intervention
and/or the provision of free condoms did not modify risky sexual behavior of
young travelers. The rate of inconsistently protected sexual relationships during
travel was however lower than expected TRIAL REGISTRATION NUMBER:
ClinicalTrials.gov: NCT01056536.
PMID- 22044611
TI - Practical aspects of a visual aid to decision making.
AB - BACKGROUND: Previous research has demonstrated that people with mild intellectual
disabilities (ID) have difficulty in 'weighing up' information, defined as
integrating disparate items of information in order to reach a decision. However,
this problem could be overcome by the use of a visual aid to decision making. In
an earlier study, participants were taught to translate information about the
pros and cons of different choices into a single evaluative dimension, by
manipulating green (good) and red (bad) bars of varying lengths (corresponding to
the value ascribed). Use of the visual calculator increased the consistency of
performance (and decreased impulsive responding) in a temporal discounting task,
and increased the amount of information that participants provided to justify
their decisions in scenario-based financial decision-making tasks. METHODS: The
present study examined some practical aspects of visual calculator training,
using a pen-and-paper version of two temporal discounting tasks. Participants
with mild ID were tested, individually and in a group setting, before and after
training in the group setting, and 2 months later. RESULTS: (i) The visual aid
improved temporal discounting performance using pen-and-paper presentation in a
group setting as effectively as previously demonstrated using computer-based
individual presentation. (ii) Following withdrawal of the aid, improvements in
temporal discounting performance were maintained at 1 day post training, but lost
following a 2-month hiatus; however, participants showed perfect retention, over
2 months, of how to use the aid. (iii) In addition to decreasing impulsivity in a
hypothetical task, as previously demonstrated, use of the visual calculator also
increased the ability of impulsive participants to wait in real time. CONCLUSION:
The results suggest that the visual calculator has practical applicability to
support decision making by people with mild ID in community settings.
PMID- 22044612
TI - Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an
endogenously activated feed-back loop in visceral inflammatory pain.
AB - BACKGROUND: Activation of proteinase-activated receptor-4 (PAR-4) from the
colonic lumen has an antinociceptive effect to colorectal distension (CRD) in
mice in basal conditions. We aimed to determine the functional localization of
the responsible receptors and to test their role in two different hyperalgesia
models. METHODS: Mice received PAR-4 activating peptide (PAR-4-AP, AYPGKF-NH(2))
or vehicle intraperitoneally (IP), and abdominal EMG response to CRD was
measured. The next group received PAR-4-AP intracolonically (IC) with or without
2,4,6-triaminopyrimidine, a chemical tight junction blocker, before CRD. The SCID
mice were used to test the role of lymphocytes in the antihyperalgesic effect.
The effects of PAR-4-AP and PAR-4-antagonist (P4pal-10) were evaluated in water
avoidance stress (WAS) model and low grade 2,4,6-trinitrobenzene sulfonic acid
(TNBS) colitis. Spinal Fos protein expression was visualized by
immunohistochemistry. KEY RESULTS: The antinociceptive effect of PAR-4-AP
disappeared when was administrered IP, or with the blockade of colonic epithelial
tight junctions, suggesting that PAR-4-AP needs to reach directly the nerve
terminals in the colon. The CRD-induced spinal Fos overexpression was reduced by
43% by PAR-4-AP. The PAR-4-AP was antihyperalgesic in both hyperalgesia models
and in mice with impaired lymphocytes. The PAR-4-antagonist significantly
increased the TNBS, but not the WAS-induced colonic hyperalgesia. CONCLUSIONS &
INFERENCES: The antinociceptive effect of PAR-4-AP depends on its penetration to
the colonic mucosa. The PAR-4 activation is endogenously involved as a feedback
loop to attenuate inflammatory colonic hyperalgesia to CRD.
PMID- 22044613
TI - Assessment of left ventricular mechanical dyssynchrony using real time three
dimensional echocardiography: a comparative study to Doppler tissue imaging.
AB - PURPOSE: To assess left ventricular mechanical dyssynchrony (LVMD) using real
time three-dimensional echocardiography (RT3DE) and comparing it with the
different dyssynchrony indices derived from Doppler tissue imaging (DTI) for the
same patient. METHODS: The study included 60 consecutive patients who were
considered candidates for CRT, i.e., having ejection fraction <=35%, NYHA class
III or ambulatory class IV, QRS duration >=120 msec, on optimal pharmacological
therapy. Apical RT3DE full volumes were obtained and analyzed to generate the
systolic dyssynchrony index (SDI-16), which is the standard deviation of the time
to minimal systolic volume of the 16 segments of LV. Color-coded DTI was
performed for the three standard apical views with estimation of the mechanical
dyssynchrony index (12 Ts-SD), which is the standard deviation of the time to
peak systolic velocity at 12 segments of LV. RESULTS: SDI-16 was 10.96 +/- 3.9%
(cutoff value: 8.3%), while Ts-SD was 38 +/- 10.2 msec (cutoff value: 32.6 msec).
The concordance rate for both indices was 75%; however, there was no correlation
between both indices (r = 0.14, P = 0.3). SDI-16 showed good correlation with QRS
duration (r = 0.45, P < 0.001) and inverse correlation with left ventricular
ejection fraction (LVEF) calculated by RT3DE (r =-0.37, P = 0.004), while 12 Ts
SD index showed no correlation with QRS duration (r =-0.0082, P = 0.51) or 2D
LVEF (r =-0.26, P = 0.84). CONCLUSIONS: RT3DE can quantify LVMD by providing the
SDI-16 and it may prove to be more useful than DTI as it shows increasing
dyssynchrony with increased QRS duration and decreased LVEF.
PMID- 22044614
TI - Discussing trainee participation in cataract surgery: what are patients told?
PMID- 22044615
TI - Survival after treatment for carcinoma invading bladder muscle: a Dutch
population-based study on the impact of hospital volume.
AB - Study Type - Prognosis (cohort). Level of Evidence 2a. What's known on the
subject? and What does the study add? The subject of mortality and survival rates
after radical cystectomies in high-volume hospitals in comparison to low-volume
hospitals has been extensively studied. Postoperative mortality is known to be
significantly lower with high-volume providers, but for survival rates there was
only a trend forwards this finding. For this reason, we performed this Dutch
population-based study on survival rates, to see if we had enough power to
support this trend with significant findings. To our knowledge, this is the first
study of good quality showing a significant beneficial effect for survival in
high-volume hospitals. OBJECTIVE: * To examine the volume-outcome relationship
for carcinoma invading bladder muscle (MIBC) with respect to differences in
survival rates among all hospitals in the Netherlands as a guide for
regionalization initiatives. MATERIALS AND METHODS: * This population-based
retrospective study included all patients (n= 13 033) newly diagnosed with MIBC
during the period 1999-2008 in the Netherlands, selected from the Netherlands
Cancer Registry. * Data were collected on demographics, morphology, stage at
diagnosis and after surgery, primary treatment, vital status and date of follow
up or death. * The relative survival rate (RSR) per treatment was analysed for
age, stage and hospital surgical volume. RESULTS: * Overall 5 and 10-year RSR for
all treatments of MIBC was 32% and 25%, respectively. * Although 71.7% of the
patients featured stages II and III, radical cystectomy was only performed in
only 42% and 44% of these patients, respectively. * Relative survival for MIBC
remained unchanged in the two consecutive time periods (1999-2003 and 2004-2008).
* In all, 34% of patients diagnosed in low-volume hospitals (<10
cystectomies/year) underwent cystectomy vs 42% of those diagnosed in high-volume
hospitals (P= 0.000). * In a multivariate analysis long-term survival (>30 days
after surgery) was significantly lower in patients after cystectomy for stage
II/III in low-volume hospitals (hazard ratio [HR] 1.17, P= 0.036). A high lymph
node count (>20) was associated with a lower risk of death (HR 0.52, P= 0.000).
CONCLUSIONS: * The 10-year RSR for patients with MIBC in the Netherlands was
modest (25%) and has remained unchanged in the last decade. * The chance of
undergoing cystectomy is significantly higher in high-volume hospitals. Long-term
survival after cystectomy is higher in high-volume hospitals. * Regionalization
of bladder cancer treatments could improve overall outcomes.
PMID- 22044616
TI - Park gazettement and integrated conservation and development as factors in
community conflict at Bwindi Impenetrable Forest, Uganda.
AB - Conflicts between protected-area managers and local people are common, but the
drivers of conflict are rarely analyzed. This limits opportunities to identify
strategies that reduce conflict and the magnitude of resulting threats to
conservation. Integrated conservation and development (ICD) was adopted at Bwindi
Impenetrable Forest, Uganda, to reduce conflict during gazettement of the
national park, but the success of this approach remains contested. We retrieved
documents of conflict written by park staff and local people from 1986 through
2000 (before, during, and after gazettement). We extracted data on 48 incidences
of violent conflict and categorized them by gazettement period, area, instigator,
and type to undertake a historical analysis of the triggers of violent conflict
at Bwindi. Before and during gazettement, local villagers instigated most of the
conflict incidents when law-enforcement efforts sought to halt commercial
activities within Bwindi. No conflict arose from the arrest of villagers
collecting subsistence resources during these periods. After gazettement,
prohibitions on commercial activities continued to drive conflict even though
villagers collecting subsistence resources were arrested more frequently than
before gazettement, and local attitudes toward the park had improved following
receipt of ICD benefits. Law-enforcement efforts targeted commercial activities
to reduce this threat to Bwindi's mountain gorillas (Gorilla beringei beringei),
although the activities remained important income sources for people in villages
near Bwindi. Losing commercial income following gazettement therefore appeared to
be their primary motivation for instigating conflict with park rangers.
Prohibitions on subsistence resource use triggered conflict less often. Our use
of typologies for a multivariate conflict analysis demonstrates that by
identifying differences between effects of conservation as drivers of conflict,
conflict analysis can enable a more strategic deployment of conflict-resolution
measures that could further conservation efforts. At Bwindi targeting ICD toward
individuals who lost benefits from commercial activities may strengthen the role
of ICD in conflict resolution and conservation.
PMID- 22044617
TI - Genetic modulation of the FV(Leiden)/normal FV ratio and risk of venous
thrombosis in factor V Leiden heterozygotes.
AB - BACKGROUND AND OBJECTIVES: The factor (F)V Leiden mutation causes activated
protein C (APC) resistance by decreasing the susceptibility of FVa to APC
mediated inactivation and by impairing the APC-cofactor activity of FV in FVIIIa
inactivation. However, APC resistance and the risk of venous thromboembolism
(VTE) vary widely among FV Leiden heterozygotes. Common F5 genetic variation
probably contributes to this variability. PATIENTS/METHODS: APC resistance was
determined in 250 FV Leiden heterozygotes and 133 normal relatives using the
prothrombinase-based assay, which specifically measures the susceptibility of
plasma FVa to APC. The effects of 12 F5 single-nucleotide polymorphisms (SNPs) on
the normalized APC sensitivity ratio (nAPCsr) and on FV levels were determined by
multiple regression analysis. RESULTS: In FV Leiden heterozygotes,VTE risk
increased with increasing nAPCsr, reaching an odds ratio (OR) of 9.9 (95%
confidence interval [CI] 1.2-80.5) in the highest nAPCsr quartile. The minor
alleles of several F5 SNPs, including 327 A/G (Q51Q), 409 G/C (D79H), 2663
A/G(K830R, T2 haplotype), 6533 T/C (M2120T) and 6755 A/G (D2194G, R2 haplotype),
increased the nAPCsr in FV Leiden heterozygotes, but not in their normal
relatives. Most of these effects could be attributed to a shift in the
FV(Leiden)/normal FV ratio. Four FV Leiden heterozygotes with extremely high
nAPCsr turned out to be pseudo-homozygotes, i.e. they carried a deleterious
mutation on the non-Leiden allele. CONCLUSIONS: In FV Leiden heterozygotes, the
prothrombinase-based nAPCsr is a marker of VTE risk and is modulated by common F5
SNPs that affect the FV(Leiden)/normal FV ratio in plasma.
PMID- 22044618
TI - Complete genomic sequence of a reovirus isolated from grass carp in China.
AB - A reovirus was isolated from sick grass carp in Guangdong, China in 2009, and
tentatively named 'grass carp reovirus Guangdong 108 strain' (GCRV-GD108). This
reovirus was propagated in grass carp snout fibroblast cell line PSF with no
obvious cytopathic effects. Its genome was 24,703bp in length with a 50% G+C
content and 11 dsRNA segments encoding 11 proteins instead of 12 proteins. It has
been classified as an Aquareovirus (AQRV). Sequence comparisons showed that it
possessed only 7 homologous proteins to grass carp reovirus (GCRV) (with 17.6
45.8% identities), but 9 homologous proteins to mammalian orthoreoviruses (MRV)
(with 15-46% identities). GCRV-GD108 lacked homology to VP7, NS4&NS5 and NS3 of
GCRV, while it had sigma1 and sigma NS homology to MRV. VP2 of GCRV-GD108 shared
high amino acid sequence identity (44-47%) with AQRVs, whereas VP5 did not
exhibit much identity (24-25%) to AQRVs. Conserved terminal sequences, 5'-GUAAUUU
and UUCAUC-3', were found in all of the 11 genomic segments of GCRV-GD108 at the
5' and 3' non-coding regions (NCRs) of the segments. The 5' NCRs of GCRV-GD108
was similar to GCRV, but differed from other species of AQRV or Orthoreoviruses
(ORV). Phylogenetic analysis of coat proteins belonging to Reoviridae, VP1-VP6,
showed that GCRV-GD108 clustered with AQRVs and grouped with ORVs, suggesting
that GCRV-GD108 belonged to the genus Aquareovirus but was distinctive from any
known species of AQRV. Morphological and pathological analyses, and genetic
characterization of GCRV-GD108 suggested that it may be a new species of AQRV and
it was more closely related with ORVs than other AQRVs. In addition, RT-PCR
analysis of diseased grass carp samples collected from different regions of China
indicated that these viruses displayed high similarities to each other (95.3
99.4%). They also shared high sequence similarities to GCRV-GD108 (96.7-99.4%),
indicating that GCRV-GD108 is representative of the prevalence strain in southern
China.
PMID- 22044619
TI - Infection of Hantaan virus strain AA57 leading to pulmonary disease in laboratory
mice.
AB - Hantaan virus (HTNV) is a causative agent of hemorrhagic fever with renal
syndrome (HFRS). The pathogenesis of HFRS has not been fully elucidated, mainly
due to the lack of a suitable animal model. In laboratory mice, HTNV causes
encephalitis. However, that symptom is dissimilar to human hantavirus infections.
We found that HTNV strain AA57 (isolated from Apodemus agrarius in Far East
Russia) caused pulmonary disease in 2-week-old ICR mice. The clinical signs of
the infected mice were piloerection, trembling, hunching, labored breathing, and
body-weight loss. A large volume of pleural effusion was collected from thoracic
cavities of the dead mice. Overall, 45% of the mice inoculated with 3000 focus
forming units (FFU) of the virus began to show clinical symptoms at 8 days post
inoculation, and 25% of the inoculated mice died within 3 days of onset of the
disease. The morbidity and mortality rates of the mice inoculated with 30
30,000FFU of HTNV strain AA57 were roughly equivalent. The highest rates of virus
positivity (11/12) and the highest titers of HTNV strain AA57 were detected in
the lungs of the dead mice, while lower detection rates and viral titers were
found in the heart, kidneys, spleen, and brain. Interstitial pneumonia,
perivascular edema, hemorrhage, inflammatory infiltration and vascular failure
were observed in the lungs of the sick mice. Hantaviral antigens were detected in
the lung endothelial cells of the sick mice. The symptoms and pathology of this
mouse model resemble those of hantavirus pulmonary syndrome (HPS) and, to a
certain extent, those of HFRS. This is the first report that, in laboratory mice,
the HFRS-related hantavirus causes a HPS-like disease and shares some symptom
similarities with HFRS.
PMID- 22044620
TI - Orally active zwitterionic factor Xa inhibitors with long duration of action.
AB - We have optimized 2-aminomethylphenylamine derivative as a factor Xa inhibitor.
Several polar functional groups were introduced in the central phenyl ring, and
we focused on zwitter ionic compound showing continuous inhibitory activity in
oral administration test. In vitro and oral activities were improved by
optimization of S1 and S4 ligands. Incorporating the interaction with S1-beta
pocket enhanced in vitro factor Xa inhibitory activity to less than 1 nM. Many
zwitter ionic compounds showed long duration of action and potent inhibitory
activity and high AUC values in oral administration tests to monkeys.
PMID- 22044621
TI - ortho-Quinone tanshinones directly inhibit telomerase through an oxidative
mechanism mediated by hydrogen peroxide.
AB - The tanshinone natural products possess a variety of pharmacological properties
including anti-bacterial, anti-inflammatory, anti-oxidant, and anti-neoplastic
activity. The molecular basis of these effects, however, remains largely unknown.
In the present study, we explored the direct effect of tanshinones on the enzyme
telomerase. Telomerase is up-regulated in the majority of cancer cells and is
essential for their survival, making it a potential anti-cancer drug target. We
found that the ortho-quinone tanshinone II-A inhibits telomerase in a time- and
DTT-dependent fashion, and the hydrogen peroxide scavenger catalase protected
telomerase from inactivation. These findings demonstrate that ortho-quinone
containing tanshinones can inhibit telomerase owing to their ability to generate
reactive oxygen species. The results also provide evidence that telomerase is
directly and negatively regulated by reactive oxygen species.
PMID- 22044624
TI - Mitochondrial-nuclear co-evolution and its effects on OXPHOS activity and
regulation.
AB - Factors required for mitochondrial function are encoded both by the nuclear and
mitochondrial genomes. The order of magnitude higher mutation rate of animal
mitochondrial DNA (mtDNA) enforces tight co-evolution of mtDNA and nuclear DNA
encoded factors. In this essay we argue that such co evolution exists at the
population and inter-specific levels and affect disease susceptibility. We also
argue for the existence of three modes of co-evolution in the mitochondrial
genetic system, which include the interaction of mtDNA and nuclear DNA encoded
proteins, nuclear protein - mtDNA-encoded RNA interaction within the
mitochondrial translation machinery and nuclear DNA encoded proteins-mtDNA
binging sites interaction in the frame of the mtDNA replication and transcription
machineries. These modes of co evolution require co-regulation of the interacting
factors encoded by the two genomes. Thus co evolution plays an important role in
modulating mitochondrial activity. This article is part of a Special Issue
entitled: Mitochondrial Gene Expression.
PMID- 22044625
TI - Immunotherapy of infections caused by rare filamentous fungi.
AB - Invasive fungal infections caused by rare filamentous fungi constitute a
significant cause of morbidity and mortality in patients with defective immune
responses. Despite the advent of new antifungal agents, the problem is escalating
as the number of susceptible hosts increases and virulent, more resistant fungal
strains emerge. There is evidence that reconstitution of the host immune function
is a major contributor to the resolution of these infections. Therapeutic
modalities aimed at increasing phagocyte numbers, such as granulocyte
transfusions, stimulating the immune response, such as administration of
haematopoietic growth factors and other proinflammatory cytokines, or indirectly
augmenting immune function have shown promising results in the preclinical
setting. Because of the rarity of the infections, multicentre clinical trials are
needed to demonstrate the efficacy and safety of the new immunomodulating
approaches.
PMID- 22044622
TI - The role of epigenetic variation in the pathogenesis of systemic lupus
erythematosus.
AB - The focus of the present review is on the extent to which epigenetic alterations
influence the development of systemic lupus erythematosus. Lupus is a systemic
autoimmune disease characterized by the production of autoantibodies directed at
nuclear self-antigens. A DNA methylation defect in CD4+ T cells has long been
observed in idiopathic and drug-induced lupus. Recent studies utilizing high
throughput technologies have further characterized the nature of the DNA
methylation defect in lupus CD4+ T cells. Emerging evidence in the literature is
revealing an increasingly interconnected network of epigenetic dysregulation in
lupus. Recent reports describe variable expression of a number of regulatory
microRNAs in lupus CD4+ T cells, some of which govern the expression of DNA
methyltransferase 1. While studies to date have revealed a significant role for
epigenetic defects in the pathogenesis of lupus, the causal nature of epigenetic
variation in lupus remains elusive. Future longitudinal epigenetic studies in
lupus are therefore needed.
PMID- 22044626
TI - Colour homogeneity and visual perception of age, health and attractiveness of
male facial skin.
AB - BACKGROUND: Visible facial skin condition in females is known to affect
perception of age, health and attractiveness. Skin colour distribution in shape-
and topography-standardized female faces, driven by localized melanin and
haemoglobin, can account for up to twenty years of apparent age perception.
Although this is corroborated by an ability to discern female age even in
isolated, non-contextual skin images, a similar effect in the perception of male
skin is yet to be demonstrated. OBJECTIVES: To investigate the effect of skin
colour homogeneity and chromophore distribution on the visual perception of age,
health and attractiveness of male facial skin. METHODS: Cropped images from the
cheeks of facial images of 160 Caucasian British men aged 10-70 years were blind
rated for age, health and attractiveness by a total of 308 participants. In
addition, the homogeneity of skin images and corresponding
eumelanin/oxyhaemoglobin concentration maps were analysed objectively using
Haralick's image segmentation algorithm. RESULTS: Isolated skin images taken from
the cheeks of younger males were judged as healthier and more attractive.
Perception of age, health and attractiveness was strongly related to melanin and
haemoglobin distribution, whereby more even distributions led to perception of
younger age and greater health and attractiveness. The evenness of melanized
features was a stronger cue for age perception, whereas haemoglobin distribution
was associated more strongly with health and attractiveness perception.
CONCLUSIONS: Male skin colour homogeneity, driven by melanin and haemoglobin
distribution, influences perception of age, health and attractiveness.
PMID- 22044627
TI - Liver fluke-induced hepatic oxysterols stimulate DNA damage and apoptosis in
cultured human cholangiocytes.
AB - Oxysterols are cholesterol oxidation products that are generated by enzymatic
reactions through cytochrome P450 family enzymes or by non-enzymatic reactions
involving reactive oxygen and nitrogen species. Oxysterols have been identified
in bile in the setting of chronic inflammation, suggesting that biliary
epithelial cells are chronically exposed to these compounds in certain clinical
settings. We hypothesized that biliary oxysterols resulting from liver fluke
infection participate in cholangiocarcinogenesis. Using gas chromatography/mass
spectrometry, we identified oxysterols in livers from hamsters infected with
Opisthorchis viverrini that develop cholangiocarcinoma. Five oxysterols were
found: 7-keto-cholesta-3,5-diene (7KD), 3-keto-cholest-4-ene (3K4), 3-keto
cholest-7-ene (3K7), 3-keto-cholesta-4,6-diene (3KD), and cholestan
3beta,5alpha,6beta-triol (Triol). Triol and 3K4 were found at significantly
higher levels in the livers of hamsters with O. viverrini-induced
cholangiocarcinoma. We therefore investigated the effects of Triol and 3K4 on
induction of cholangiocarcinogenesis using an in vitro human cholangiocyte
culture model. Triol- and 3K4-treated cells underwent apoptosis. Western blot
analysis showed significantly increased levels of Bax and decreased levels of Bcl
2 in these cells. Increased cytochrome c release from mitochondria was found
following treatment with Triol and 3K4. Triol and 3K4 also induced formation of
the DNA adducts 1,N(6)-etheno-2'-deoxyadenosine, 3,N(4)-etheno-2'-deoxycytidine
and 8-oxo-7,8-dihydro-2'-deoxyguanosine in cholangiocytes. The data suggest that
Triol and 3K4 cause DNA damage via oxidative stress. Chronic liver fluke
infection increases production of the oxysterols Triol and 3K4 in the setting of
chronic inflammation in the biliary system. These oxysterols induce apoptosis and
DNA damage in cholangiocytes. Insufficient and impaired DNA repair of such
mutated cells may enhance clonal expansion and further drive the change in
cellular phenotype from normal to malignant.
PMID- 22044628
TI - Helicobacter pylori vacuolating toxin A and apoptosis.
AB - VacA, the vacuolating cytotoxin A of Helicobacter pylori, induces apoptosis in
epithelial cells of the gastic mucosa and in leukocytes. VacA is released by the
bacteria as a protein of 88 kDa. At the outer surface of host cells, it binds to
the sphingomyelin of lipid rafts. At least partially, binding to the cells is
facilitated by different receptor proteins. VacA is internalized by a clathrin
independent mechanism and initially accumulates in GPI-anchored proteins-enriched
early endosomal compartments. Together with early endosomes, VacA is distributed
inside the cells. Most of the VacA is eventually contained in the membranes of
vacuoles. VacA assembles in hexameric oligomers forming an anion channel of low
conductivity with a preference for chloride ions. In parallel, a significant
fraction of VacA can be transferred from endosomes to mitochondria in a process
involving direct endosome-mitochondria juxtaposition. Inside the mitochondria,
VacA accumulates in the mitochondrial inner membrane, probably forming similar
chloride channels as observed in the vacuoles. Import into mitochondria is
mediated by the hydrophobic N-terminus of VacA. Apoptosis is triggered by loss of
the mitochondrial membrane potential, recruitment of Bax and Bak, and release of
cytochrome c.
PMID- 22044629
TI - Identifying features of bipolarity in patients with first-episode postpartum
depression: findings from the international BRIDGE study.
AB - OBJECTIVES: The aims of this study were to assess rates of bipolar spectrum
disorders in women experiencing their first episode of postpartum depression, and
to find out features indicative of bipolarity in these patients. METHODS: As part
of the international BRIDGE study designed to detect hypo/mania in patients with
a major depressive episode, 52 (5.85%) were found to experience a first episode
of postpartum (FEPP) depression, whereas 833 (94.13%) had a first episode of
nonpostpartum (FENPP) depression. Hypo/mania was assessed using varying
definitions of bipolarity, and the two groups compared on sociodemographic,
family history and clinical characteristics. RESULTS: Compared to FENPP
depressive patients, women with FEPP depression had higher rates of bipolar
disorders, with more hypo/mania in first degree relatives. Psychotic symptoms,
atypical features, mixed depression, younger age at onset, high number of prior
episodes, episodes of short duration, switches on antidepressants, seasonality of
mood episodes as well as mood episodes with free intervals were found to be more
frequent in FEPP depressives. LIMITATIONS: The following are the limitations of
this study: centres not randomly selected, recall bias, cross-sectional design,
and limited training of participating psychiatrists. CONCLUSIONS: This study
confirms, in women experiencing a first depressive episode, high rates (15 to
50%) of bipolar disorders during the postpartum period and is the first to
systematically assess and demonstrate the higher prevalence of identifying
features of bipolarity in FEPP versus FENPP depression. Early recognition of
bipolarity in these patients may help prevent the harmful consequences of this
illness.
PMID- 22044630
TI - Negative affectivity moderated by BDNF and stress response.
AB - BACKGROUND: Gene*environment (G*E) interactions are known to predict
susceptibility to disorders such as depression and anxiety. Adverse experiences
in childhood and number of stressful life events (SLEs) have been widely studied
as environmental risk factors; however, SLE response has not yet been studied.
Here we present a first attempt at the analysis of the interaction between the
response to personal and academic stressful events during different life stages
and the gene polymorphisms 5-HTTLPR, 5-HTTVNTR (STin2), HTR1A C(-1019)G, and BDNF
Val66Met in the prediction of negative affectivity (NA). METHODS: Standardized
questionnaires (ST-DEP and STAI) were used to measure negative affectivity
derived from depression and anxiety in a sample of 303 undergraduate students.
Response to stressful events during childhood, high school and college years was
evaluated together with a self-report personal history form. Multiple logistic
regression analysis was used to perform association and G*E analysis. RESULTS:
Negative affectivity is strongly associated with childhood maltreatment and
stress response. Gene associations were observed between 5-HTTVNTR allele 12 and
the S_12 haplotype with NA derived from high scores in both depression and
anxiety. The BDNF gene variant was not associated with NA derived from depression
or anxiety alone, but it was associated with the comorbid presentation. A
significant G*E interaction was observed between the BDNF Val66Met and stress
response during childhood and college years although the risk for negative
affectivity conferred by stress response during childhood was only significant
among the Met allele carriers, while stress response during college years was a
significant risk factor regardless of the BDNF Val66Met genotype. A significant
G*E interaction was also found between the HTR1A C(-1019)G variant and childhood
maltreatment. LIMITATIONS: The study has two main limitations, sample size is low
and retrospective recognition of SLEs is a concern. CONCLUSION: Altogether, our
results demonstrate that the BDNF Val66Met variant moderates the effect of stress
during both childhood and college years; although this effect seems to be more
critical during childhood given that the risk conferred by childhood stress was
restricted to the Met allele carriers. We also found that the HTR1A C(-1019)G
variant moderates the effect of childhood maltreatment in our study population.
PMID- 22044631
TI - Distinguishing symptom dimensions of depression and anxiety: an integrative
approach.
AB - BACKGROUND: Clark and Watson developed the tripartite model in which a symptom
dimension of 'negative affect' covers common psychological distress that is
typically seen in anxious and depressed patients. The 'positive affect' and
'somatic arousal' dimensions cover more specific symptoms. Although the model has
met much support, it does not cover all relevant anxiety symptoms and its
negative affect dimension is rather unspecific. Therefore, we aimed to extend the
tripartite model in order to describe more specific symptom patterns with
unidimensional measurement scales. METHOD: 1333 outpatients provided self report
data. To develop an extended factor model, exploratory factor analysis (EFA) was
conducted in one part of the data (n=578). Confirmatory factor analysis (CFA) was
conducted in the second part (n=755), to assess model-fit and comparison with
other models. Rasch analyses were done to investigate the unidimensionality of
the factors. RESULTS: EFA resulted in a 6-factor model: feelings of
worthlessness, fatigue, somatic arousal, anxious apprehension, phobic fear and
tension. CFA in the second sample showed that a 6-factor model with a
hierarchical common severity factor fits the data better than alternative 1- and
3-factor models. Rasch analyses showed that each of the factors and the total of
factors can be regarded as unidimensional measurement scales. LIMITATIONS: The
model is based on a restricted symptom-pool: more dimensions are likely to exist.
CONCLUSION: The extended tripartite model describes the clinical state of
patients more specifically. This is relevant for both clinical practice and
research.
PMID- 22044632
TI - Spatial heterogeneity, frequency-dependent selection and polymorphism in host
parasite interactions.
AB - BACKGROUND: Genomic and pathology analysis has revealed enormous diversity in
genes involved in disease, including those encoding host resistance and parasite
effectors (also known in plant pathology as avirulence genes). It has been
proposed that such variation may persist when an organism exists in a spatially
structured metapopulation, following the geographic mosaic of coevolution. Here,
we study gene-for-gene relationships governing the outcome of plant-parasite
interactions in a spatially structured system and, in particular, investigate the
population genetic processes which maintain balanced polymorphism in both
species. RESULTS: Following previous theory on the effect of heterogeneous
environments on maintenance of polymorphism, we analysed a model with two demes
in which the demes have different environments and are coupled by gene flow.
Environmental variation is manifested by different coefficients of natural
selection, the costs to the host of resistance and to the parasite of virulence,
the cost to the host of being diseased and the cost to an avirulent parasite of
unsuccessfully attacking a resistant host. We show that migration generates
negative direct frequency-dependent selection, a condition for maintenance of
stable polymorphism in each deme. Balanced polymorphism occurs preferentially if
there is heterogeneity for costs of resistance and virulence alleles among
populations and to a lesser extent if there is variation in the cost to the host
of being diseased. We show that the four fitness costs control the natural
frequency of oscillation of host resistance and parasite avirulence alleles. If
demes have different costs, their frequencies of oscillation differ and when
coupled by gene flow, there is amplitude death of the oscillations in each deme.
Numerical simulations show that for a multiple deme island model, costs of
resistance and virulence need not to be present in each deme for stable
polymorphism to occur. CONCLUSIONS: Our theoretical results confirm the
importance of empirical studies for measuring the environmental heterogeneity for
genetic costs of resistance and virulence alleles. We suggest that such studies
should be developed to investigate the generality of this mechanism for the long
term maintenance of genetic diversity at host and parasite genes.
PMID- 22044633
TI - Genome-wide dynamic changes of DNA methylation of repetitive elements in human
embryonic stem cells and fetal fibroblasts.
AB - DNA methylation changes in repetitive elements (REs) are associated with the
regulation of gene transcription, embryonic development, differentiation and
carcinogenesis. However, genome-wide analysis of DNA methylation of human REs is
lacking. Here, we performed genome-wide methylation analysis of REs in nine
repeat types in human embryonic stem cells (H1) and fetal fibroblasts (IMR90),
and found that the potential for changes in the DNA methylation of REs was
different among the nine repeat types and within different genomic regions. DNA
methylation changes in the nine repeat types were related to the GC content and
CpG density of the sequence contexts. The differentially methylated REs and
targeted genes of different repeat types were associated with gene silencing in
the transition from H1 to IMR90 cells. Our results suggest that a quarter of REs
are involved in the reprogramming of DNA methylation which may play important
epigenetic roles during cellular differentiation.
PMID- 22044634
TI - Projection to latent pathways (PLP): a constrained projection to latent variables
(PLS) method for elementary flux modes discrimination.
AB - BACKGROUND: Elementary flux modes (EFM) are unique and non-decomposable sets of
metabolic reactions able to operate coherently in steady-state. A metabolic
network has in general a very high number of EFM reflecting the typical
functional redundancy of biological systems. However, most of these EFM are
either thermodynamically unfeasible or inactive at pre-set environmental
conditions. RESULTS: Here we present a new algorithm that discriminates the
"active" set of EFM on the basis of dynamic envirome data. The algorithm merges
together two well-known methods: projection to latent structures (PLS) and EFM
analysis, and is therefore termed projection to latent pathways (PLP). PLP has
two concomitant goals: (1) maximisation of correlation between EFM weighting
factors and measured envirome data and (2) minimisation of redundancy by
eliminating EFM with low correlation with the envirome. CONCLUSIONS: Overall, our
results demonstrate that PLP slightly outperforms PLS in terms of predictive
power. But more importantly, PLP is able to discriminate the subset of EFM with
highest correlation with the envirome, thus providing in-depth knowledge of how
the environment controls core cellular functions. This offers a significant
advantage over PLS since its abstract structure cannot be associated with the
underlying biological structure.
PMID- 22044635
TI - Clinical indicators of bacterial meningitis among neonates and young infants in
rural Kenya.
AB - BACKGROUND: Meningitis is notoriously difficult to diagnose in infancy because
its clinical features are non-specific. World Health Organization (WHO)
guidelines suggest several indicative signs, based on limited data. We aimed to
identify indicators of bacterial meningitis in young infants in Kenya, and
compared their performance to the WHO guidelines. We also examined the
feasibility of developing a scoring system for meningitis. METHODS: We studied
all admissions aged < 60 days to Kilifi District Hospital, 2001 through 2005. We
evaluated clinical indicators against microbiological findings using likelihood
ratios. We prospectively validated our findings 2006 through 2007. RESULTS: We
studied 2,411 and 1,512 young infants during the derivation and validation
periods respectively. During derivation, 31/1,031 (3.0%) neonates aged < 7 days
and 67/1,380 (4.8%) young infants aged 7-59 days (p < 0.001) had meningitis. 90%
of cases could be diagnosed macroscopically (turbidity) or by microscopic
leukocyte counting. Independent indicators of meningitis were: fever,
convulsions, irritability, bulging fontanel and temperature >= 39 degrees C.
Areas under the receiver operating characteristic curve in the validation period
were 0.62 [95%CI: 0.49-0.75] age < 7 days and 0.76 [95%CI: 0.68-0.85] thereafter
(P = 0.07), and using the WHO signs, 0.50 [95%CI 0.35-0.65] age < 7 days and 0.82
[95%CI: 0.75-0.89] thereafter (P = 0.0001). The number needed to LP to identify
one case was 21 [95%CI: 15-35] for our signs, and 28 [95%CI: 18-61] for WHO
signs. With a scoring system, a cut-off of >= 1 sign offered the best compromise
on sensitivity and specificity. CONCLUSION: Simple clinical signs at admission
identify two thirds of meningitis cases in neonates and young infants. Lumbar
puncture is essential to diagnosis and avoidance of unnecessary treatment, and is
worthwhile without CSF biochemistry or bacterial culture. The signs of Meningitis
suggested by the WHO perform poorly in the first week of life. A scoring system
for meningitis in this age group is not helpful.
PMID- 22044636
TI - Exploring the biological basis of haemophilic joint disease: experimental
studies.
AB - Haemophilia has been recognized as the most severe among the inherited disorders
of blood coagulation since the beginning of the first millennium. Joint damage is
the hallmark of the disease. Despite its frequency and severity, the pathobiology
of blood-induced joint disease remains obscure. Although bleeding into the joint
is the ultimate provocation, the stimulus within the blood inciting the process
and the mechanisms by which bleeding into a joint results in synovial
inflammation (synovitis) and cartilage and bone destruction (arthropathy) is
unknown. Clues from careful observation of patient material, supplemented with
data from animal models of joint disease provide some clues as to the
pathogenesis of the process. Among the questions that remain to be answered are
the following: (i) What underlies the phenotypic variability in bleeding patterns
of patients with severe disease and the development of arthropathy in some but
not all patients with joint bleeding? (ii) What is the molecular basis underlying
the variability? (iii) Are there strategies that can be developed to counter the
deleterious effects of joint bleeding and prevent blood-induced joint disease?
Understanding the key elements, genetic and/or environmental, that are necessary
for the development of synovitis and arthropathy may lead to rational design of
therapy for the targeted prevention and treatment of blood-induced joint disease.
PMID- 22044637
TI - Benchmarks for flexible and rigid transcription factor-DNA docking.
AB - BACKGROUND: Structural insight from transcription factor-DNA (TF-DNA) complexes
is of paramount importance to our understanding of the affinity and specificity
of TF-DNA interaction, and to the development of structure-based prediction of TF
binding sites. Yet the majority of the TF-DNA complexes remain unsolved despite
the considerable experimental efforts being made. Computational docking
represents a promising alternative to bridge the gap. To facilitate the study of
TF-DNA docking, carefully designed benchmarks are needed for performance
evaluation and identification of the strengths and weaknesses of docking
algorithms. RESULTS: We constructed two benchmarks for flexible and rigid TF-DNA
docking respectively using a unified non-redundant set of 38 test cases. The test
cases encompass diverse fold families and are classified into easy and hard
groups with respect to the degrees of difficulty in TF-DNA docking. The major
parameters used to classify expected docking difficulty in flexible docking are
the conformational differences between bound and unbound TFs and the interaction
strength between TFs and DNA. For rigid docking in which the starting structure
is a bound TF conformation, only interaction strength is considered. CONCLUSIONS:
We believe these benchmarks are important for the development of better
interaction potentials and TF-DNA docking algorithms, which bears important
implications to structure-based prediction of transcription factor binding sites
and drug design.
PMID- 22044638
TI - Node-positive renal cell carcinoma in the absence of distant metastases:
predictors of cancer-specific mortality in a population-based cohort.
AB - Nodal metastases, even in the absence of distant metastases, portend a bad
prognosis. The percentage of positive nodes (PPN) represents an important
predictor of cancer-specific mortality (CSM) in patients in the group T(any) N(1)
M(0) . In consequence, universal inclusion of PPN should be considered in
prospective and retrospective CSM analyses. OBJECTIVES: To examine the outcomes
of patients with node-positive renal cell carcinoma (RCC) in the absence of
distant metastases in a large population-based cohort of patients To examine the
ability of standard risk factors to predict cancer-specific mortality (CSM).
PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results
database, a total of 799 patients with RCC nodal metastases and absence of
distant metastases undergoing nephrectomy were identified. Univariable and
multivariable analyses was performed with the aim of identifying independent
predictors of CSM in this cohort of patients. Specifically, we examined the
effect of the number of removed nodes (NRN), the number of positive nodes (NPN)
and the percentage of positive nodes (PPN) on CSM. RESULTS: Actuarial survival
estimates showed that 53.2, 37.8 and 25.7% of patients survived at 24, 60 and 120
months after nephrectomy. In Kaplan-Meier analyses, NRN failed to clearly
discriminate between recorded CSM rates (log rank P = 0.07). Discrimination was
noted when CSM was stratified according to NPN (log rank P = 0.02) and PPN (log
rank P = 0.001). In multivariable analyses, age, Fuhrman grade, histological
subtype, T stage and PPN were independent predictors of CSM. CONCLUSIONS: Our
data indicate that CSM of patients with exclusive nodal metastases differs
according to PPN. Consequently, PPN warrants consideration in future prognostic
schemes.
PMID- 22044639
TI - Left atrial metastases of poorly differentiated thyroid carcinoma diagnosed by
echocardiography and magnetic resonance imaging--case report and review of
literature.
AB - Intracardiac metastases of thyroid carcinoma are a rare event. Their incidence is
low in large autopsy series, and antemortem diagnosis is even less common. We
present the case of a woman with advanced poorly differentiated thyroid carcinoma
who had extensive intracardiac metastases. This case highlights the usefulness of
echocardiography and magnetic resonance imaging in the diagnosis and differential
diagnosis of cardiac metastases.
PMID- 22044640
TI - Further improvements on the factors affecting bone mineral density measured by
quantitative micro-computed tomography.
AB - The effects of imaging parameters and special configuration of objects within the
reconstruction space on the micro computed tomography (MUCT) based mineral
density have been explored, and a series of density correction curves have been
presented. A manufacturer-provided calibration phantom (0, 100, 200, 400, 800 mg
HA/cm(3)) was imaged at all possible imaging conditions (n=216) based on energy,
resolution, vial diameter, beam hardening correction factor and averaging. For
each imaging condition, a linear regression model was fitted to the observed
versus expected densities, and the intercepts (beta(0)) and slopes (beta(1)) of
the regression lines and each density level were modeled using multiple
regression modeling. Additionally, a custom made phantom (0, 50, 150, 500, 800,
1000 and 1500 mg HA/cm(3)) was scanned in order to study the effects of location
and orientation of an object within the reconstruction space and presence of
surrounding objects on MUCT based mineral density. The energy, vial diameter and
beam hardening correction factor were significant predictors of cumineral density
(P values<0.001), while averaging and resolution did not have a significant
effect on the observed density values (P values>0.1) except for 0.0 density (P
values<0.04). Varying the location of an object within the reconstruction space
from the center to the periphery resulted in a drop in observed mineral density
up to 10% (P values<0.005). The presence of surrounding densities resulted in
decreased observed mineral density up to 17% at the center and up to 14% at the
periphery of the reconstruction space (P values<0.001 for all densities).
Changing the orientation of the sample also had a significant effect on the
observed mineral density, resulting in up to 16% lower observed mineral density
for vertical vs. horizontal orientation at the center of the reconstruction space
(P value<0.001). We conclude that energy, resolution and post processing
correction factor are significant predictors of the observed mineral density in
MUCT.
PMID- 22044642
TI - The influence of systemic therapy on the serum levels of IL-6 and IL-8 in
pemphigus vulgaris.
AB - BACKGROUND: The place of cell-mediated immunity and cytokines in the
immunopathogenesis of pemphigus vulgaris (PV) has not been fully established.
OBJECTIVE: To assess the serum levels of pro-inflammatory cytokines, Interleukine
6 (IL-6) and Interleukine-8 (IL-8), in PV patients before and after therapy, to
evaluate the influence of therapy on the serum cytokine levels. METHODS: Sixty
six newly diagnosed PV patients enrolled into the study. The serum levels of IL-8
and IL-6 were measured in 66 and 64 patients, respectively. According to the
extent of skin and mucosal involvement, the patients were divided into two groups
namely mild and severe. The serum levels of cytokines were measured using enzyme
linked immunosorbent assay (ELISA) method before and after 4 weeks of
prednisolone plus azathioprine therapy. RESULTS: In 64 patients studied for the
serum level of IL-6, the median IL-6 level was significantly decreased from 1.6
to 0.9 pg/mL by therapy (P-value = 0.001). Segregating the patients according to
the severity of the disease, the serum level of IL-6 did not differ significantly
by therapy in patients with a mild disease. However, in patients with a severe
disease the median serum level of IL-6 decreased significantly from 1.8 to 0.9
pg/mL after therapy (P-value = 0.001). No significant changes were found in the
IL-8 level by treatment. CONCLUSION: The significant decrease in the IL-6 level
after therapy suggests that blocking of IL-6 could have therapeutic benefits for
the treatment of PV, particularly in severe forms.
PMID- 22044641
TI - Bacterial communities in sediments of the shallow Lake Dongping in China.
AB - AIMS: The purpose of this study was to discuss how the environmental inputs and
anthropogenic activities impact bacterial communities in the sediments of a
shallow, eutrophic and temperate freshwater lake. METHODS AND RESULTS: Sediment
cores were collected from Lake Dongping, located in Taian, Shandong, China. All
samples were processed within 4 h of collection. Total nitrogen, total phosphorus
(TP), total organic carbon, ammonium nitrogen and nitrate nitrogen content of
samples were measured by Kjeldahl determination, sulphuric acid-perchloric acid
digestion and molybdenum blue colorimetry, potassium dichromate titration,
Nessler's reagent colorimetric and the phenol disulphonic acid colorimetric
method, respectively. Seasonal and temporal diversity of sediment bacterial
communities at six stations in Lake Dongping were investigated using molecular
approaches (terminal restriction fragment length polymorphism and 16S rDNA clone
libraries). Noticeable seasonal and temporal variations were observed in
bacterial diversity and composition at all six stations. Sediment bacterial
communities in Lake Dongping belonged to 16 phyla: Proteobacteria (including
alpha-Proteobacteria, beta-Proteobacteria, delta-Proteobacteria, epsilon
Proteobacteria, gamma-Proteobacteria), Acidobacteria, Planctomycetes,
Bacteroidetes, Firmicutes, Verrucomicrobia, Nitrospira, Chloroflexi,
Gemmatimonadetes, Chlorobi, Cyanobacteria, Deferribacteres, Actinobacteria, OP8,
Spirochaetes and OP11. Members of beta-, delta- and gamma-Proteobacterial
sequences were predominant in 11 of 12 clone libraries derived from sediment
samples. Sediment samples collected at stations 1 and 4 in July had the greatest
bacterial diversity while those collected at station 2 in October had the least
diversity. TP concentration was significantly correlated with the distribution of
bacterial communities. CONCLUSIONS: Our results suggested that different
environmental nutrient inputs contribute to seasonal and temporal variations of
chemical features and bacterial communities in sediments of Lake Dongping. TP
concentration was significantly correlated with the distribution of bacterial
communities. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has an important
implication for the optimization of integrated ecosystem assessment of shallow
temperate freshwater lake and provides interesting information for the subsequent
of the ecosystem.
PMID- 22044643
TI - Assessing the impact of a Christmas advertisement campaign on Catalan wine
preference using Choice Experiments.
AB - Our paper seeks to assess the impact of information and advertisement on
consumers' preference for wines in special occasions (Christmas) in Catalonia
(Spain). We apply the Choice Experiments method to study the relative importance
of attributes that describe consumers' decision to purchase wine by using the
Heteroskedastic Extreme Value (HEV) model. Data were obtained from two
questionnaires applied to a pre and post spot samples formed by 299 and 400
individuals, respectively. Results suggest that the proposed spot does not affect
the ranking of the preferred attributes, nevertheless this preference is
heterogeneous. After advertising preferences scores have revealed significant
differences. The relative importance of the "Catalan" wine has increased compared
to the "Spanish" wine. The most preferred product is a Catalan wine made from the
"Cabernet Sauvignon" variety. Wines that have been previously tasted by the
consumer seem to be preferred over recommended or prestigious wines. However,
advertising increases the relative importance of prestigious wines.
PMID- 22044645
TI - Expression of platelet-bound stromal cell-derived factor-1 in patients with non
valvular atrial fibrillation and ischemic heart disease.
AB - AIMS: Blood cell infiltration and inflammation are involved in atrial remodelling
during atrial fibrillation (AF) although the exact mechanisms of inflammatory
cell recruitment remain poorly understood. Platelet-bound stromal cell-derived
factor-1 (SDF-1) is increased in cases of ischemic myocardium and regulates
recruitment of CXCR4(+) cells on the vascular wall. Whether platelet-bound SDF-1
expression is differentially influenced by non-valvular paroxysmal or permanent
atrial fibrillation (AF) in patients with stable angina pectoris (SAP) or acute
coronary syndrome (ACS) has not been reported so far. METHODS AND RESULTS: A
total of 1291 consecutive patients with coronary artery disease (CAD) undergoing
coronary angiography were recruited. Among the patients with SAP, platelet-bound
SDF-1 is increased in patients with paroxysmal AF compared with SR or to
persistent/permanent AF (P < 0.05 for both). Platelet-bound SDF-1 correlated with
plasma SDF-1 (r = 0.488, P = 0.013) in patients with AF and ACS, which was more
pronounced among patients with persistent AF (r = 0.842, P = 0.009). Plasma SDF-1
was increased in persistent/permanent AF compared with SR. Patients with ACS
presented with enhanced platelet-bound-SDF-1 compared with SAP. Interestingly,
among patients with ACS, patients with paroxysmal or persistent/permanent AF
presented with an impaired platelet-bound SDF-1 expression compared with patients
with SR. CONCLUSIONS: Differential expression of platelet-bound and plasma SDF-1
was observed in patients with AF compared with SR which may be involved in
progenitor cell mobilization and inflammatory cell recruitment in patients with
AF and ischemic heart disease. Further in vivo studies are required to elucidate
the role of SDF-1 in atrial remodeling and the atrial fibrillation course.
PMID- 22044644
TI - Plasma proteomic profiles from disease-discordant monozygotic twins suggest that
molecular pathways are shared in multiple systemic autoimmune diseases.
AB - INTRODUCTION: Although systemic autoimmune diseases (SAID) share many clinical
and laboratory features, whether they also share some common features of
pathogenesis remains unclear. We assessed plasma proteomic profiles among
different SAID for evidence of common molecular pathways that could provide
insights into pathogenic mechanisms shared by these diseases. METHODS:
Differential quantitative proteomic analyses (one-dimensional reverse-phase
liquid chromatography-mass spectrometry) were performed to assess patterns of
plasma protein expression. Monozygotic twins (four pairs discordant for systemic
lupus erythematosus, four pairs discordant for juvenile idiopathic arthritis and
two pairs discordant for juvenile dermatomyositis) were studied to minimize
polymorphic gene effects. Comparisons were also made to 10 unrelated, matched
controls. RESULTS: Multiple plasma proteins, including acute phase reactants,
structural proteins, immune response proteins, coagulation and transcriptional
factors, were differentially expressed similarly among the different SAID
studied. Multivariate Random Forest modeling identified seven proteins whose
combined altered expression levels effectively segregated affected vs. unaffected
twins. Among these seven proteins, four were also identified in univariate
analyses of proteomic data (syntaxin 17, alpha-glucosidase, paraoxonase 1, and
the sixth component of complement). Molecular pathway modeling indicated that
these factors may be integrated through interactions with a candidate plasma
biomarker, PON1 and the pro-inflammatory cytokine IL-6. CONCLUSIONS: Together,
these data suggest that different SAID may share common alterations of plasma
protein expression and molecular pathways. An understanding of the mechanisms
leading to the altered plasma proteomes common among these SAID may provide
useful insights into their pathogeneses.
PMID- 22044646
TI - Meta-analysis of susceptibility of woody plants to loss of genetic diversity
through habitat fragmentation.
AB - Shrubs and trees are assumed less likely to lose genetic variation in response to
habitat fragmentation because they have certain life-history characteristics such
as long lifespans and extensive pollen flow. To test this assumption, we
conducted a meta-analysis with data on 97 woody plant species derived from 98
studies of habitat fragmentation. We measured the weighted response of four
different measures of population-level genetic diversity to habitat fragmentation
with Hedge's d and Spearman rank correlation. We tested whether the genetic
response to habitat fragmentation was mediated by life-history traits (longevity,
pollination mode, and seed dispersal vector) and study characteristics (genetic
marker and plant material used). For both tests of effect size habitat
fragmentation was associated with a substantial decrease in expected
heterozygosity, number of alleles, and percentage of polymorphic loci, whereas
the population inbreeding coefficient was not associated with these measures. The
largest proportion of variation among effect sizes was explained by pollination
mechanism and by the age of the tissue (progeny or adult) that was genotyped. Our
primary finding was that wind-pollinated trees and shrubs appeared to be as
likely to lose genetic variation as insect-pollinated species, indicating that
severe habitat fragmentation may lead to pollen limitation and limited gene flow.
In comparison with results of previous meta-analyses on mainly herbaceous
species, we found trees and shrubs were as likely to have negative genetic
responses to habitat fragmentation as herbaceous species. We also found that the
genetic variation in offspring was generally less than that of adult trees, which
is evidence of a genetic extinction debt and probably reflects the genetic
diversity of the historical, less-fragmented landscape.
PMID- 22044647
TI - Attention in action: evidence from on-line corrections in left visual neglect.
AB - It is widely accepted that the posterior parietal cortex is critical for the on
line control of action and optic ataxia patients are unable to correct their
movements in-flight to changes in target position. The current study investigated
on-line correction in patients with left visual neglect, right brain damaged
patients without neglect and healthy controls. Participants were asked to reach
towards a central target that could jump unexpectedly, at movement onset, to the
right or left sides of space. In response to the jump, participants were asked
either to follow the target or to stop their movement. Neglect patients were able
to correct their ongoing movements smoothly and accurately towards right and left
target jumps. They did so even when told to stop their movement, indicating that
these corrections occurred automatically (i.e., without instruction). However,
the timing of corrections to the left was delayed in neglect patients and this
produced a drastic increase in movement time. To our surprise, we also found that
neglect patients were impaired at stopping their ongoing reaches, when compared
to the control groups, in response to either left or right jump trials. We
suggest that the 'automatic pilot' system for the hand is spared in neglect, but
its processing speed is unilaterally slowed due to a deficit in orienting of
attention to the contralesional side. We relate these findings to the breakdown
of a system that combines information for attention, perception and action.
Damage to this system may not only slow corrective movements to the
contralesional side, but also produce non-lateralized deficits in interrupting an
ongoing reach.
PMID- 22044648
TI - A "concrete view" of aging: event related potentials reveal age-related changes
in basic integrative processes in language.
AB - Normal aging is accompanied by changes in both structural and functional cerebral
organization. Although verbal knowledge seems to be relatively stable across the
lifespan, there are age-related changes in the rapid use of that knowledge during
on-line language processing. In particular, aging has been linked to reduce
effectiveness in preparing for upcoming words and building an integrated sentence
level representation. The current study assessed whether such age-related changes
extend even to much simpler language units, such as modification relations
between a centrally presented adjective and a lateralized noun. Adjectives were
used to elicit concrete and abstract meanings of the same, polysemous lexical
items (e.g., "green book" vs. "interesting book"). Consistent with findings that
lexical information is preserved with age, older adults, like younger adults,
exhibited concreteness effects at the adjectives, with more negative responses to
concrete adjectives over posterior (300-500 ms; N400) and frontal (300-900 ms)
channels. However, at the noun, younger adults exhibited concreteness-based
predictability effects linked to left hemisphere processing and imagery effects
linked to right hemisphere processing, contingent on whether the adjectives and
nouns formed a cohesive conceptual unit. In contrast, older adults showed neither
effect, suggesting that they were less able to rapidly link the adjective-noun
meaning to form an integrated conceptual representation. Age-related changes in
language processing may thus be more pervasive than previously realized.
PMID- 22044649
TI - Nouns referring to tools and natural objects differentially modulate the motor
system.
AB - While increasing evidence points to a critical role for the motor system in
language processing, the focus of previous work has been on the linguistic
category of verbs. Here we tested whether nouns are effective in modulating the
motor system and further whether different kinds of nouns - those referring to
artifacts or natural items, and items that are graspable or ungraspable - would
differentially modulate the system. A Transcranial Magnetic Stimulation (TMS)
study was carried out to compare modulation of the motor system when subjects
read nouns referring to objects which are Artificial or Natural and which are
Graspable or Ungraspable. TMS was applied to the primary motor cortex
representation of the first dorsal interosseous (FDI) muscle of the right hand at
150 ms after noun presentation. Analyses of Motor Evoked Potentials (MEPs)
revealed that across the duration of the task, nouns referring to graspable
artifacts (tools) were associated with significantly greater MEP areas. Analyses
of the initial presentation of items revealed a main effect of graspability. The
findings are in line with an embodied view of nouns, with MEP measures modulated
according to whether nouns referred to natural objects or artifacts (tools),
confirming tools as a special class of items in motor terms. Additionally our
data support a difference for graspable versus non graspable objects, an effect
which for natural objects is restricted to initial presentation of items.
PMID- 22044650
TI - Effects of transcranial direct current stimulation (tDCS) on behaviour and
electrophysiology of language production.
AB - Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left
dorsal prefrontal cortex (DPFC) has been shown to improve language production.
The present study examined neurophysiological underpinnings of this effect. In a
single-blinded within-subject design, we traced effects of A-tDCS compared to
sham stimulation over the left DPFC using electrophysiological and behavioural
correlates during overt picture naming. Online effects were examined during A
tDCS by employing the semantic interference (SI-)Effect - a marker that denotes
the functional integrity of the language system. The behavioural SI-Effect was
found to be reduced, whereas the electrophysiological SI-Effect was enhanced over
left compared to right temporal scalp-electrode sites. This modulation is
suggested to reflect a superior tuning of neural responses within language
related generators. After -(offline) effects of A-tDCS were detected in the delta
frequency band, a marker of neural inhibition. After A-tDCS there was a reduction
in delta activity during picture naming and the resting state, interpreted to
indicate neural disinhibition. Together, these findings demonstrate
electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest
that A-tDCS is capable of enhancing neural processes during and after
application. The present functional and oscillatory neural markers could detect
positive effects of prefrontal A-tDCS, which could be of use in the neuro
rehabilitation of frontal language functions.
PMID- 22044651
TI - Working memory and amnesia: the role of stimulus novelty.
AB - Despite the traditional view that damage to the hippocampus and/or surrounding
areas of the medial temporal lobe (MTL) does not impair short-term or working
memory (WM), recent research has shown MTL amnesics to be impaired on WM tasks
that require maintaining a small amount of information over brief retention
intervals (e.g., maintenance of a single face for one second). However, the types
of tasks that have demonstrated WM impairments in amnesia tend to have involved
novel stimuli. We hypothesized that WM may be impaired in amnesia for tasks that
require maintaining novel information, but may be preserved for more familiar
material, particularly if the material can be easily rehearsed. To test this
hypothesis, patient HC, a 22-year-old developmental amnesic with relatively
preserved semantic memory and 20 age and education matched controls performed a
delayed match-to-sample task that required maintaining a single famous or non
famous face for 1-8s, digit span and reading span tasks, and a modified Brown
Peterson task that required maintaining a single high- or low-frequency word or a
non-word for 4-8s. HC's performance was impaired for non-famous faces but
preserved for famous faces, impaired for the reading span task but preserved for
digit span, and it was impaired for non-words and unfamiliar low-frequency words
but preserved for familiar words. These results support the hypothesis that an
intact hippocampus is necessary for maintaining a single novel stimulus in WM.
However, stimulus familiarity and rehearsal support WM via cortical regions
independent of the MTL.
PMID- 22044652
TI - Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and
invasive growth of gastric epithelial cells.
AB - Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of
Helicobacter pylori (H. pylori) infected gastric epithelial cells leading to cell
migration and invasive growth. Considering the cellular mechanisms, the type IV
secretion system (T4SS) and the effector protein cytotoxin-associated gene A
(CagA) of H. pylori are well-studied initiators of distinct signal transduction
pathways in host cells targeting kinases, adaptor proteins, GTPases, actin
binding and other proteins involved in the regulation of the actin lattice. In
this review, we summarize recent findings of how H. pylori functionally interacts
with the complex signaling network that controls the actin cytoskeleton of motile
and invasive gastric epithelial cells.
PMID- 22044653
TI - Sleep in children and adolescents with Angelman syndrome: association with parent
sleep and stress.
AB - BACKGROUND: Sleep concerns are common in children with Angelman syndrome, with 20
80% of individuals having a decreased sleep need and/or abnormal sleep-wake
cycles. The impact of these sleep behaviours on parental sleep and stress is not
known. METHOD: Through the use of standardised questionnaires, wrist actigraphy
and polysomnography, we defined the sleep behaviours of 15 children/adolescents
with Angelman syndrome and the association of the child/adolescents sleep
behaviours on parental sleep behaviours and parental stress. RESULTS: Both
children/adolescents and their parents exhibited over 1 h of wake time after
sleep onset and fragmented sleep. Prolonged sleep latency in the child was
associated with parent insomnia and daytime sleepiness. Additionally, variability
in child total sleep time was associated with parental stress. CONCLUSIONS: Poor
sleep in children/adolescents with Angelman syndrome was associated with poor
parental sleep and higher parental stress. Further work is warranted to identify
the underlying causes of the poor sleep, and to relate these findings to daytime
functioning, behaviour and the family unit.
PMID- 22044654
TI - Optic disc haemorrhage and posterior vitreous haemorrhage from an acute posterior
vitreous detachment.
PMID- 22044655
TI - A focus on shoulders.
PMID- 22044656
TI - Synthesis and in vitro evaluation of analogues of avocado-produced toxin (+)-(R)
persin in human breast cancer cells.
AB - A structure-activity study of several new synthetic analogues of the avocado
produced toxin persin has been conducted, with compounds being evaluated for
their cytostatic and pro-apoptotic effects in human breast cancer cells. A 4
pyridinyl derivative demonstrated activity comparable to that of the natural
product, suggesting future directions for exploration of structure-activity
relationships.
PMID- 22044657
TI - Diversity of metalloproteinases in Bothrops neuwiedi snake venom transcripts:
evidences for recombination between different classes of SVMPs.
AB - BACKGROUND: Snake venom metalloproteinases (SVMPs) are widely distributed in
snake venoms and are versatile toxins, targeting many important elements involved
in hemostasis, such as basement membrane proteins, clotting proteins, platelets,
endothelial and inflammatory cells. The functional diversity of SVMPs is in part
due to the structural organization of different combinations of catalytic,
disintegrin, disintegrin-like and cysteine-rich domains, which categorizes SVMPs
in 3 classes of precursor molecules (PI, PII and PIII) further divided in 11
subclasses, 6 of them belonging to PII group. This heterogeneity is currently
correlated to genetic accelerated evolution and post-translational modifications.
RESULTS: Thirty-one SVMP cDNAs were full length cloned from a single specimen of
Bothrops neuwiedi snake, sequenced and grouped in eleven distinct sequences and
further analyzed by cladistic analysis. Class P-I and class P-III sequences
presented the expected tree topology for fibrinolytic and hemorrhagic SVMPs,
respectively. In opposition, three distinct segregations were observed for class
P-II sequences. P-IIb showed the typical segregation of class P-II SVMPs.
However, P-IIa grouped with class P-I cDNAs presenting a 100% identity in the 365
bp at their 5' ends, suggesting post-transcription events for interclass
recombination. In addition, catalytic domain of P-IIx sequences segregated with
non-hemorrhagic class P-III SVMPs while their disintegrin domain grouped with
other class P-II disintegrin domains suggesting independent evolution of
catalytic and disintegrin domains. Complementary regions within cDNA sequences
were noted and may participate in recombination either at DNA or RNA levels.
Proteins predicted by these cDNAs show the main features of the correspondent
classes of SVMP, but P-IIb and P-IIx included two additional cysteines cysteines
at the C-termini of the disintegrin domains in positions not yet described.
CONCLUSIONS: In B. neuwiedi venom gland, class P-II SVMPs were represented by
three different types of transcripts that may have arisen by interclass
recombination with P-I and P-III sequences after the divergence of the different
classes of SVMPs. Our observations indicate that exon shuffling or post
transcriptional mechanisms may be driving these recombinations generating new
functional possibilities for this complex group of snake toxins.
PMID- 22044658
TI - Pulmonary complications of pneumococcal community-acquired pneumonia: incidence,
predictors, and outcomes.
AB - The aim of this study was to evaluate the clinical characteristics, predictors
and outcomes of pneumococcal pneumonia developing pulmonary complications and the
distribution of pneumococcal serotypes. It was a prospective study including all
adult patients admitted to the Hospital Clinic of Barcelona, Spain (2001-2009)
with the diagnosis of pneumococcal pneumonia. Microbiological investigation was
systematically performed, including antimicrobial susceptibility and serotype
distribution (only invasive strains isolated during 2006-2009). Complicated
pneumonia was defined as the presence of one or more pulmonary complications:
pleural effusion, empyema, or multilobar infiltrates. We included 626 patients,
and 235 (38%) had the following pulmonary complications: pleural effusion, 122
(52%); empyema, 18 (8%); and multilobar infiltration, 151 (64%). Forty-six (20%)
patients had more than one complication. Patients with pulmonary complications
showed a higher rate of intensive-care unit admission (34% vs. 13%, p <0.001), a
higher rate of shock (16% vs. 7%, p <0.001), a longer length of stay (9 days vs.
6 days, p <0.001), and a lower rate of penicillin resistance (14% vs. 25%, p
0.013), but similar mortality (9% vs. 8%). No significant differences were
observed in the serotype distribution between complicated and uncomplicated
pneumonia. Chronic obstructive pulmonary disease (COPD) (OR 0.38, 95% CI 0.23
0.63; p <0.001) was a protective factor against pulmonary complications, whereas
chronic liver disease (OR 3.60, 95% CI 1.71-7.60; p 0.001), admission C-reactive
protein level >=18 mg/dL (OR 2.77, 95% CI 1.91-4.00; p <0.001) and admission
creatinine level >1.5 mg/dL (OR 2.01, 95% CI 1.31-3.08; p 0.001) were risk
factors for pulmonary complications. Complicated pneumonia was characterized by a
more severe clinical presentation, but was not associated with increased
mortality. Resistance to antibiotics was lower in complicated cases. No
significant differences were observed in the serotype distribution between
complicated and uncomplicated pneumonia. In the multivariate analysis, COPD was a
protective factor against pulmonary complications.
PMID- 22044659
TI - Effects of intracellular superoxide removal at acupoints with TAT-SOD on obesity.
PMID- 22044660
TI - Association between 8-oxo-7,8-dihydroguanine excretion and risk of lung cancer in
a prospective study.
AB - Oxidative damage to guanine (8-oxoGua) is one of the most abundant lesions
induced by oxidative stress and documented mutagenic. 8-Oxoguanine DNA
glycosylase 1 (OGG1) removes 8-oxoGua from DNA by excision. The urinary excretion
of 8-oxoGua is a biomarker of exposure, reflecting the rate of damage in the
steady state. The aim of this study was to investigate urinary 8-oxoGua as a risk
factor for lung cancer. In a nested case-cohort design we examined associations
between urinary excretion of 8-oxoGua and risk of lung cancer as well as
potential interaction with the OGG1 Ser326Cys polymorphism in a population-based
cohort of 25,717 men and 27,972 women aged 50-64 years with 3-7 years follow-up.
We included 260 cases with lung cancer and a subcohort of 263 individuals matched
on sex, age, and smoking duration for comparison. Urine collected at entry was
analysed for 8-oxoGua by HPLC with electrochemical detection. There was no
significant effect of smoking or OGG1 genotype on the excretion of 8-oxoGua.
Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer
was 1.06 (0.97-1.15) per doubling of 8-oxoGua excretion. The association between
lung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17
(1.03-1.31)], never-smokers [IRR: 9.94 (1.04-94.7)], and former smokers [IRR:
1.19 (1.07-1.33)]. There was no significant interaction with the OGG1 genotype,
although the IRR was 1.14 (0.98-1.34) among subjects homozygous for Cys326. The
association between urinary 8-oxoGua excretion and lung cancer risk among former
and never-smokers suggests that oxidative stress with damage to DNA is important
in this group.
PMID- 22044661
TI - Effect of 12 months of testosterone replacement therapy on metabolic syndrome
components in hypogonadal men: data from the Testim Registry in the US (TRiUS).
AB - BACKGROUND: Recent evidence suggests that there may be a bidirectional,
physiological link between hypogonadism and metabolic syndrome (MetS), and
testosterone replacement therapy (TRT) has been shown to improve some symptoms of
MetS in small patient populations. We examined the effect of 12 months of TRT on
MetS components in a large cohort of hypogonadal men. METHODS: Data were obtained
from TRiUS (Testim(r) Registry in the United States), a 12-month, multicenter,
prospective observational registry (N = 849) of hypogonadal men prescribed Testim
1% testosterone gel (5-10 g/day). Data analyzed included age, total testosterone
(TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and MetS
components: waist circumference, blood pressure, fasting blood glucose, plasma
triglycerides, and HDL cholesterol. RESULTS: Of evaluable patients (581/849) at
baseline, 37% were MetS+ (n = 213) and 63% were MetS- (n = 368). MetS+ patients
had significantly lower TT (p < 0.0001) and SHBG (p = 0.01) levels. Patients with
the lowest quartile TT levels (<206 ng/dL [<7.1 nmol/L]) had a significantly
increased risk of MetS+ classification vs those with highest quartile TT levels
(>=331 ng/dL [>=11.5 nmol/L]) (odds ratio 2.66; 95% CI, 1.60 to 4.43). After 12
months of TRT, TT levels significantly increased in all patients (p < 0.005).
Despite having similar TT levels after TRT, only MetS+ patients demonstrated
significant decreases in waist circumference, fasting blood glucose levels, and
blood pressure; lowest TT quartile patients demonstrated significant decreases in
waist circumference and fasting blood glucose. Neither HDL cholesterol nor
triglyceride levels changed significantly in either patient population.
CONCLUSION: Hypogonadal MetS+ patients were more likely than their MetS-
counterparts to have lower baseline TT levels and present with more comorbid
conditions. MetS+ patients and those in the lowest TT quartile showed improvement
in some metabolic syndrome components after 12 months of TRT. While it is
currently unclear if further cardiometabolic benefit can be seen with longer TRT
use in this population, testing for low testosterone may be warranted in MetS+
men with hypogonadal symptoms.
PMID- 22044662
TI - Healthcare resource utilization among haemophilia A patients in the United
States.
AB - Advances in therapy have improved life expectancy and quality of life of patients
with haemophilia A. Due to the chronic and complex management of this disease,
particularly, the development of inhibitors, little is known about their health
resource utilization in the real-life setting over time. The aim was to assess
the distribution and trend of healthcare resource utilization among US
haemophilia A patients with and without inhibitors. The MarketScan(r) Database,
was queried to identify individuals with >=1 year continuous enrolment, two
medical diagnoses of haemophilia A and claims for factor VIII or bypassing agent
(to infer inhibitor status) during 2001-2007. Haemophilia-related cost was
estimated from inpatient, outpatient and pharmacy claims. Annual cost differences
were assessed by age and over a 4-year period for those with continuous
enrolment. Among 51 million covered lives, 1044 haemophilia patients were
identified, of whom 981 (94%; mean age = 21.2 years) did not have an inhibitor.
The median haemophilia-related cost for these patients was $63,935 per patient
per year. When normalized by weight, annual cost was stable (no statistically
significant differences) among 312 non-inhibitor patients (mean age = 21.8 years)
with 4-year continuous data. While there was a wide distribution of haemophilia
related cost among the 63 individuals with an inhibitor (mean age = 15.4 years),
only 0.6% of the total haemophilia patients had costs exceeding $1 million per
patient per year. This study indicated that most haemophilia A patients were
inhibitor-free with relatively stable annual costs over time. There was a wide
distribution of haemophilia-related cost for inhibitor patients, while the
proportion of patients who incurred extreme high cost was low.
PMID- 22044663
TI - Outcomes of clomiphene citrate treatment in young hypogonadal men.
AB - Study Type - Therapy (case series) Level of Evidence 4. What's known on the
subject? and What does the study add? Hypogonadism is a prevalent problem,
increasing in frequency as men age. It is most commonly treated by testosterone
supplementation therapy but in younger patients this can lead to testicular
atrophy with subsequent exogenous testosterone dependency and may impair
spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment
in these patients with hypogonadism when maintenance of fertility is desired.
This study shows that CC is a safe and efficacious drug to use as an alternative
to exogenous testosterone. Not only have we validated previous findings of other
papers but have proven our findings over a much longer period (mean duration of
treatment 19 months). This prospective study is the largest to date assessing
both the objective hormone response to CC therapy as well as the subjective
response based on a validated questionnaire. OBJECTIVE: * To prospectively assess
the andrological outcomes of long-term clomiphene citrate (CC) treatment in
hypogonadal men. PATIENTS AND METHODS: * We prospectively evaluated 86 men with
hypogonadism (HG) as confirmed by two consecutive early morning testosterone
measurements <300 ng/dL. * The cohort included all men with HG presenting to our
clinic between 2002 and 2006 who, after an informed discussion, elected to have
CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every
other day. The target testosterone level was 550 +/- 50 ng/dL. * Testosterone
(free and total), sex hormone binding globulin, oestradiol, luteinizing hormone
and follicle stimulating hormone were measured at baseline and during treatment
on all patients. Once the desired testosterone level was achieved,
testosterone/gonadotropin levels were measured twice per year. * To assess
subjective response to treatment, the androgen deficiency in aging males (ADAM)
questionnaire was administered before treatment and during follow-up. RESULTS: *
Patients' mean (standard deviation [sd]; range) age was 29 (3; 22-37) years.
Infertility was the most common reason (64%) for seeking treatment. The mean (sd)
duration of CC treatment was 19 (14) months. * At the last evaluation, 70% of men
were using 25 mg CC every other day, and the remainder were using 50 mg every
other day. * All mean testosterone and gonadotropin measurements significantly
increased during treatment. * Subjectively, there was an improvement in all
questions (except loss of height) on the ADAM questionnaire. More than half the
patients had an improvement in at least three symptoms. * There were no major
side effects recorded and the presence of a varicocele did not have an impact on
the response to CC. CONCLUSION: * Long-term follow-up of CC treatment for HG
shows that it appears to be an effective and safe alternative to testosterone
supplementation in men wishing to preserve their fertility.
PMID- 22044664
TI - The evolution of metabolic networks of E. coli.
AB - BACKGROUND: Despite the availability of numerous complete genome sequences from
E. coli strains, published genome-scale metabolic models exist only for two
commensal E. coli strains. These models have proven useful for many applications,
such as engineering strains for desired product formation, and we sought to
explore how constructing and evaluating additional metabolic models for E. coli
strains could enhance these efforts. RESULTS: We used the genomic information
from 16 E. coli strains to generate an E. coli pangenome metabolic network by
evaluating their collective 76,990 ORFs. Each of these ORFs was assigned to one
of 17,647 ortholog groups including ORFs associated with reactions in the most
recent metabolic model for E. coli K-12. For orthologous groups that contain an
ORF already represented in the MG1655 model, the gene to protein to reaction
associations represented in this model could then be easily propagated to other
E. coli strain models. All remaining orthologous groups were evaluated to see if
new metabolic reactions could be added to generate a pangenome-scale metabolic
model (iEco1712_pan). The pangenome model included reactions from a metabolic
model update for E. coli K-12 MG1655 (iEco1339_MG1655) and enabled development of
five additional strain-specific genome-scale metabolic models. These additional
models include a second K-12 strain (iEco1335_W3110) and four pathogenic strains
(two enterohemorrhagic E. coli O157:H7 and two uropathogens). When compared to
the E. coli K-12 models, the metabolic models for the enterohemorrhagic
(iEco1344_EDL933 and iEco1345_Sakai) and uropathogenic strains (iEco1288_CFT073
and iEco1301_UTI89) contained numerous lineage-specific gene and reaction
differences. All six E. coli models were evaluated by comparing model predictions
to carbon source utilization measurements under aerobic and anaerobic conditions,
and to batch growth profiles in minimal media with 0.2% (w/v) glucose. An
ancestral genome-scale metabolic model based on conserved ortholog groups in all
16 E. coli genomes was also constructed, reflecting the conserved ancestral core
of E. coli metabolism (iEco1053_core). Comparative analysis of all six strain
specific E. coli models revealed that some of the pathogenic E. coli strains
possess reactions in their metabolic networks enabling higher biomass yields on
glucose. Finally the lineage-specific metabolic traits were compared to the
ancestral core model predictions to derive new insight into the evolution of
metabolism within this species. CONCLUSION: Our findings demonstrate that a
pangenome-scale metabolic model can be used to rapidly construct additional E.
coli strain-specific models, and that quantitative models of different strains of
E. coli can accurately predict strain-specific phenotypes. Such pangenome and
strain-specific models can be further used to engineer metabolic phenotypes of
interest, such as designing new industrial E. coli strains.
PMID- 22044665
TI - Epidemiology and cost of herpes zoster and postherpetic neuralgia among patients
treated in primary care centres in the Valencian community of Spain.
AB - BACKGROUND: Data on the epidemiology and costs related to herpes zoster (HZ) and
postherpetic neuralgia (PHN) in Spain are scarce; therefore, studies are needed
to evaluate the epidemiological and economic impact of HZ and its most common
complication, PHN. The present study aimed to estimate the clinical and economic
burden of HZ and PHN in Valencia (Spain). METHODS: We prospectively analyzed the
burden of HZ and PHN and their attributable costs in patients from 25 general
practices in the Autonomous Community of Valencia serving 36,030 persons aged >
14 years. All patients with a clinical diagnosis of HZ who attended these centers
between December 1st 2006 and November 30th 2007 were asked to participate.
Patients included were followed for 1 year. RESULTS: Of the 130 cases of HZ
followed up, continued pain was experienced by 47.6% (95% confidence interval
(CI) = 35.6-56.7%) at 1 month after rash onset, by 14.5% (95% CI = 7.8-1.2%) at 3
months, by 9.0% (95% CI = 3.7-14.3%) at 6 months, and by 5.9% (95% CI = 1.5
10.3%) at 12 months. The percentage of patients with PHN increased with age, from
21.4% (95% CI = 8.3-40) in patients < 50 years to 59.2% (95% CI = 44.4-74) in
patients >= 70 years. The estimated total cost for the 130 HZ cases during the
follow-up period was ?49,160 ($67,349). Mean cost per patient was ?378 (range 53
2,830) ($517, range 73-3,877). CONCLUSIONS: This study shows that PHN is a
relatively common complication of HZ and that both conditions combined give rise
to a significant clinical and economic burden for patients and providers.
PMID- 22044666
TI - High resistance of Isaria fumosorosea to carbendazim arises from the
overexpression of an ATP-binding cassette transporter (ifT1) rather than tubulin
mutation.
AB - AIMS: Probing possible mechanisms involved in the resistance of entomopathogenic
fungus Isaria fumosorosea to carbendazim fungicide. METHODS AND RESULTS: A
carbendazim-sensitive strain (If116) selected from 15 wild-type strains was
subjected to NaNO(2) -induced mutagenesis, yielding nine mutants with carbendazim
resistance increased by 82- to 830-fold and thermotolerance decreased by 15-51%.
Comparing the protein sequences deduced from the alpha- and beta-tubulin genes of
If116 and its mutants revealed no traceable site mutation relating to the
enhanced resistance although the transcripts levels of beta-tubulin gene in all
mutants were 0.87- to 7.16-fold of that in If116. Three examined mutants showed
multidrug resistance because they were significantly more resistant to
glufosinate, imidacloprid and other six fungicides than If116 during growth.
Further examination of rhodamine-stained blastospores revealed existence of drug
efflux pump protein(s) in all carbendazim-resistant mutants. Thus, the sequences
of an ATP-binding cassette (ABC) transporter gene (ifT1) and its promoter region
cloned from the wild-type and mutant strains were analysed. Three common point
mutations were located, respectively, at the binding sites of Gal4, Abf1 and Raf,
which are crucial transcription factors in the regulative network of numerous
protein loci. Such point mutations elevated the ifT1 expression by 17 to 137-fold
in all the mutants. CONCLUSIONS: The overexpression of the ABC transporter caused
by the point mutations at the binding sites was responsible for the fungal
resistance to various pesticides including carbendazim. SIGNIFICANCE AND IMPACT
OF STUDY: The transporter-mediated multidrug resistance found for the first time
in entomopathogenic fungi is potential for use in improving mycoinsecticide
compatibility with chemical pesticides.
PMID- 22044667
TI - Association between olfactory receptor genes, eating behavior traits and
adiposity: results from the Quebec Family Study.
AB - Obesity is a major health problem that can be influenced by eating behaviors.
Evidence suggests that the sensory properties of food influence eating behaviors
and lead to overeating and overweight. A previous genome-wide linkage scan for
eating behavior traits assessed with the Three-Factor Eating Questionnaire
(cognitive dietary restraint, disinhibition and hunger) performed in the Quebec
Family Study (QFS) revealed a quantitative trait locus for disinhibition on
chromosome 19p13. This region encodes a cluster of seven olfactory receptor (OR)
genes, including OR7D4, previously associated with odor perceptions. Direct
sequencing of the OR7D4 gene revealed 16 sequence variants. Nine OR7D4 sequence
variants with minor allele frequency (MAF)>1% as well as 100 SNPs spanning the
cluster of OR genes on 19p13 were tested for association with age- and sex
adjusted eating behaviors as well as adiposity traits in 890 subjects. One OR7D4
sequence variant (rs2878329 G>A) showed evidence of association with reduced
levels of adiposity (p=0.03), cognitive dietary restraint (p=0.05) and
susceptibility to hunger (p=0.008). None of the OR7D4 SNPs was associated with
disinhibition, but a SNP (rs2240927) in another OR gene (OR7E24) showed evidence
of association (p=0.03). Another SNP in the OR7G3 gene (rs10414255) was also
found to be associated with adiposity and eating behaviors. These results are the
first to suggest that variations in human olfactory receptor genes can influence
eating behaviors and adiposity. The associations reported in the present study
should be interpreted with caution considering the number of tests performed and
considered as potential new hypotheses about the effects OR polymorphisms on
eating behaviors and obesity that need to be further explored in other
populations.
PMID- 22044668
TI - Inverse correlation of free and immune complex-sequestered anti-ADAMTS13
antibodies in a patient with acquired thrombotic thrombocytopenic purpura.
PMID- 22044669
TI - The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and
inhibits tumor formation.
AB - BACKGROUND & AIMS: The kinase Akt mediates resistance of pancreatic cancer (PaCa)
cells to death and is constitutively active (phosphorylated) in cancer cells.
Whereas the kinases that activate Akt are well characterized, less is known about
phosphatases that dephosporylate and thereby inactivate it. We investigated
regulation of Akt activity and cell death by the phosphatases PHLPP1 and PHLPP2
in PaCa cells, mouse models of PaCa, and human pancreatic ductal adenocarcinoma
(PDAC). METHODS: We measured the effects of PHLPP overexpression or knockdown
with small interfering RNAs on Akt activation and cell death. We examined
regulation of PHLPPs by growth factors and reactive oxygen species, as well as
associations between PHLPPs and tumorigenesis. RESULTS: PHLPP overexpression
inactivated Akt, whereas PHLPP knockdown increased phosphorylation of Akt in PaCa
cells. Levels of PHLPPs were greatly reduced in human PDAC and in mouse genetic
and xenograft models of PaCa. PHLPP activities in PaCa cells were down-regulated
by growth factors and Nox4 reduced nicotinamide adenine dinucleotide phosphate
oxidase. PHLPP1 selectively dephosphorylated Akt2, whereas PHLPP2 selectively
dephosphorylated Akt1. Akt2, but not Akt1, was up-regulated in PDAC, and Akt2
levels correlated with mortality. Consistent with these results, high levels of
PHLPP1, which dephosphorylates Akt2 (but not PHLPP2, which dephosphorylates
Akt1), correlated with longer survival times of patients with PDAC. In mice,
xenograft tumors derived from PaCa cells that overexpress PHLPP1 (but not PHLPP2)
had inactivated Akt, greater extent of apoptosis, and smaller size. CONCLUSIONS:
PHLPP1 has tumor suppressive activity and might represent a therapeutic or
diagnostic tool for PDAC.
PMID- 22044671
TI - A single administration of the GnRH antagonist acyline inhibits basal and GnRH
stimulated serum testosterone concentrations in male dogs.
AB - The objective of this study was to describe testosterone (T) response to GnRH
challenge in antagonist-treated dogs over a 30-day period. Eight mongrel dogs
were randomly assigned to either the GnRH antagonist acyline 330 MUg/kg sc (ACY;
n = 4) or a placebo group (PLA; n = 4). The dogs were serially challenged with
the GnRH agonist, buserelin 0.2 MUg/kg sc on days -1, 1, 3, 7, 10, 14, 21 and 30.
On these days, blood samples for T determinations were collected before (-30 min)
and 60, 120 and 180 min after the agonist injection. Basal (-30 min) and post
GnRH agonist stimulation T values were compared by anova for repeated measures.
Before treatments (day -1), there were no differences in basal T serum
concentrations between groups (p > 0.1). After treatments, basal T showed a
significant interaction between treatment and day (p < 0.05). Furthermore, when
both groups were analysed independently, basal T varied in the ACY (p < 0.01) but
not in the PLA group (p > 0.1). On day -1, before treatments, the stimulation
tests had only a time effect (p = 0.05) although on days 1 (p < 0.01), 3 (p <
0.01), 7 (p < 0.01), 10 (p < 0.01) and 14 (p < 0.05), the response to the agonist
differed between groups, becoming similar on days 21 (p > 0.05) and 30 (p >
0.05). It was concluded that, in dogs, a single administration of the GnRH
antagonist prevented canine gonadal axis to physiologically respond to agonistic
challenge during 14 days.
PMID- 22044670
TI - Inflammation and disruption of the mucosal architecture in claudin-7-deficient
mice.
AB - BACKGROUND & AIMS: Integrity of the intestinal epithelium is required for
nutrition absorption and defense against pathogens. Claudins are cell adhesion
molecules that localize at tight junctions (TJs); many are expressed in the
intestinal tract, but little is known about their functions. Claudin-7 is unique
in that it has a stronger basolateral membrane distribution than other claudins,
which localize primarily to apical TJs in the intestinal epithelium. We
investigated the basolateral functions of claudin-7 and assessed the effects of
disruption of Cldn7 in intestines of mice. METHODS: We generated Cldn7(-/-) mice
and examined their intestines by histology, molecular and cellular biology, and
biochemistry approaches. We performed gene silencing experiments in epithelial
cell lines using small interfering RNAs (siRNAs). RESULTS: The Cldn7(-/-) mice
had severe intestinal defects that included mucosal ulcerations, epithelial cell
sloughing, and inflammation. Intestines of Cldn7(-/-) mice produced significantly
higher levels of cytokines, the nuclear factor kappaB p65 subunit, and
cyclooxygenase 2; they also up-regulated expression of matrix metalloproteinases
(MMPs)-3 and -7. siRNA in epithelial cell lines showed that the increased
expression of MMP-3 resulted directly from claudin-7 depletion, whereas that of
MMP-7 resulted from inflammation. Electron microscopy analysis showed that
intestines of Cldn7(-/-) mice had intercellular gaps below TJs and cell matrix
loosening. Deletion of Cldn7 reduced expression and altered localization of the
integrin alpha2 subunit in addition to disrupting formation of complexes of
claudin-7, integrin alpha2, and claudin-1 that normally form in epithelial
basolateral compartments of intestines. CONCLUSIONS: In mice, claudin-7 has non
TJ functions, including maintenance of epithelial cell-matrix interactions and
intestinal homeostasis.
PMID- 22044672
TI - Effects of acute and chronic treatment elicited by lamotrigine on behavior,
energy metabolism, neurotrophins and signaling cascades in rats.
AB - The present study was aimed to investigate the behavioral and molecular effects
of lamotrigine. To this aim, Wistar rats were treated with lamotrigine (10 and 20
mg/kg) or imipramine (30 mg/kg) acutely and chronically. The behavior was
assessed using forced swimming test. Brain-derived neurotrophic factor (BDNF),
nerve growth factor (NGF), Proteina Kinase B (PKB, AKT), glycogen synthase kinase
3 (GSK-3) and B-cell lymphoma 2 (Bcl-2) levels, citrate synthase, creatine kinase
and mitochondrial chain (I, II, II-III and IV) activities were assessed in the
brain. The results showed that both treatments reduced the immobility time. The
BDNF were increased in the prefrontal after acute treatment with lamotrigine (20
mg/kg), and the BDNF and NGF were increased in the prefrontal after chronic
treatment with lamotrigine in all doses. The AKT increased and Bcl-2 and GSK-3
decreased after both treatments in all brain areas. The citrate synthase and
creatine kinase increased in the amygdala after acute treatment with imipramine.
Chronic treatment with imipramine and lamotrigine (10 mg/kg) increased the
creatine kinase in the hippocampus. The complex I was reduced and the complex II,
II-III and IV were increased, but related with treatment and brain area. In
conclusion, lamotrigine exerted antidepressant-like, which can be attributed to
its effects on pathways related to depression, such as neurotrophins, metabolism
energy and signaling cascade.
PMID- 22044673
TI - Pulmonary function and left ventricular mass in African Americans: the
Atherosclerosis Risk in Communities (ARIC) study.
AB - PURPOSE: Impaired pulmonary function has been associated with increased
cardiovascular disease incidence and mortality. The objective of this study was
to investigate associations between pulmonary function and left ventricular (LV)
mass. METHODS: Participants were African American women (n = 1,069) and men (n =
555) aged 49-73 years, from the Atherosclerosis Risk in Communities study. Mean
pulmonary function values at the first (1987-1989) and second (1990-1992)
examinations were used. Echocardiograms were performed at the third and early in
the fourth examinations (1993-1996). Analysis of covariance and linear regression
were used to assess associations. RESULTS: Mean levels of LV mass decreased with
increasing quintiles of forced expiratory volume in one second (FEV(1) ) among
female never smokers (P = 0.039). Forced vital capacity (FVC) showed stronger
associations than FEV(1) with LV mass. Among men, LV mass was positively
associated with FEV(1) among current and never smokers, and with FVC among never
smokers. Additional analyses among never smokers revealed significant inverse
associations between LV mass and FVC among women with waist-to-hip ratios of
>0.85 and those with no history of diabetes. In contrast, significant positive
associations between LV mass and FVC were seen among male never smokers with body
mass index (BMI) of <=24.9 kg/m(2) , waist-to-hip ratios of <=0.95, no history of
hypertension or diabetes, and <=60 years old. BMI and waist-to-hip ratio
significantly modified associations among men. CONCLUSIONS: Among never smokers,
LV mass and pulmonary function were inversely associated among women and
positively associated among men. Further studies are warranted.
PMID- 22044674
TI - Antibiosis of vineyard ecosystem fungi against food-borne microorganisms.
AB - Fermentation extracts from fungi isolated from vineyard ecosystems were tested
for antimicrobial activities against a set of test microorganisms, including five
food-borne pathogens (Staphylococcus aureus EP167, Acinetobacter baumannii
(clinically isolated), Pseudomonas aeruginosa PAO1, Escherichia coli O157:H7
(CECT 5947) and Candida albicans MY1055) and two probiotic bacteria
(Lactobacillus plantarum LCH17 and Lactobacillus brevis LCH23). A total of 182
fungi was grown in eight different media, and the fermentation extracts were
screened for antimicrobial activity. A total of 71 fungi produced extracts active
against at least one pathogenic microorganism, but not against any probiotic
bacteria. The Gram-positive bacterium S. aureus EP167 was more susceptible to
antimicrobial fungi broth extracts than Gram-negative bacteria and pathogenic
fungi. Identification of active fungi based on internal transcribed spacer rRNA
sequence analysis revealed that species in the orders Pleosporales, Hypocreales
and Xylariales dominated. Differences in antimicrobial selectivity were observed
among isolates from the same species. Some compounds present in the active
extracts were tentatively identified by liquid chromatography-mass spectrometry.
Antimicrobial metabolites produced by vineyard ecosystem fungi may potentially
limit colonization and spoilage of food products by food-borne pathogens, with
minimal effect on probiotic bacteria.
PMID- 22044675
TI - Takotsubo cardiomyopathy has a unique cardiac biomarker profile: NT
proBNP/myoglobin and NT-proBNP/troponin T ratios for the differential diagnosis
of acute coronary syndromes and stress induced cardiomyopathy.
AB - BACKGROUND: Takotsubo cardiomyopathy (TC) usually is not recognized until heart
catheterization reveals typical wall motion abnormalities in the absence of
significant coronary artery disease. It was our aim to identify TC by its unique
cardiac biomarker profile at an early stage and, preferably, with non-invasive
procedures only. METHODS: Ratios of N-terminal prohormone of brain natriuretic
peptide (NT-proBNP) and myoglobin, NT-proBNP and troponin T (TnT), NT-proBNP and
creatinekinase-MB (CK-MB) were compared in patients with TC (n=39), patients with
ST-elevation myocardial infarction (STEMI, n=48) and patients with non-ST
elevation myocardial infarction (NSTEMI, n=34). Biomarkers were recorded serially
at admission and at the three consecutive days. Optimal cut-off values to
distinguish TC from STEMI and NSTEMI were calculated with receiver operator
characteristic (ROC) curves. RESULTS: At admission a NT-proBNP (ng/l)/myoglobin
(MUg/l) ratio of 3.8, distinguished TC from STEMI (sensitivity: 89%, specificity:
90%), while a NT-proBNP (ng/l)/myoglobin (MUg/l) ratio of 14 separated well
between TC and NSTEMI (sensitivity: 65%, specificity: 90%). Best differentiation
of TC and ACS was possible with the ratio of peak levels of NT-proBNP (ng/l)/TnT
(MUg/l). A cut-off value of NT-proBNP (ng/l)/TnT (MUg/l) ratio of 2889,
distinguished TC from STEMI (sensitivity: 91%, specificity: 95%), while a NT
proBNP (ng/l)/TnT (MUg/l) ratio of 5000 separated well between TC and NSTEMI
(sensitivity: 83%, specificity: 95%). CONCLUSIONS: TC goes along with a singular
cardiac biomarker profile, which might be useful to identify patients with TC
among patients presenting with acute coronary syndromes (ACS).
PMID- 22044676
TI - In vivo and in silico determination of essential genes of Campylobacter jejuni.
AB - BACKGROUND: In the United Kingdom, the thermophilic Campylobacter species C.
jejuni and C. coli are the most frequent causes of food-borne gastroenteritis in
humans. While campylobacteriosis is usually a relatively mild infection, it has a
significant public health and economic impact, and possible complications include
reactive arthritis and the autoimmune diseases Guillain-Barre syndrome. The rapid
developments in "omics" technologies have resulted in the availability of diverse
datasets allowing predictions of metabolism and physiology of pathogenic micro
organisms. When combined, these datasets may allow for the identification of
potential weaknesses that can be used for development of new antimicrobials to
reduce or eliminate C. jejuni and C. coli from the food chain. RESULTS: A
metabolic model of C. jejuni was constructed using the annotation of the NCTC
11168 genome sequence, a published model of the related bacterium Helicobacter
pylori, and extensive literature mining. Using this model, we have used in silico
Flux Balance Analysis (FBA) to determine key metabolic routes that are essential
for generating energy and biomass, thus creating a list of genes potentially
essential for growth under laboratory conditions. To complement this in silico
approach, candidate essential genes have been determined using a whole genome
transposon mutagenesis method. FBA and transposon mutagenesis (both this study
and a published study) predict a similar number of essential genes (around 200).
The analysis of the intersection between the three approaches highlights the
shikimate pathway where genes are predicted to be essential by one or more
method, and tend to be network hubs, based on a previously published
Campylobacter protein-protein interaction network, and could therefore be targets
for novel antimicrobial therapy. CONCLUSIONS: We have constructed the first
curated metabolic model for the food-borne pathogen Campylobacter jejuni and have
presented the resulting metabolic insights. We have shown that the combination of
in silico and in vivo approaches could point to non-redundant, indispensable
genes associated with the well characterised shikimate pathway, and also genes of
unknown function specific to C. jejuni, which are all potential novel
Campylobacter intervention targets.
PMID- 22044677
TI - Light and portable novel device for diabetic retinopathy screening.
AB - BACKGROUND: To validate the use of an economical portable multipurpose ophthalmic
imaging device, EyeScan (Ophthalmic Imaging System, Sacramento, CA, USA), for
diabetic retinopathy screening. DESIGN: Evaluation of a diagnostic device.
PARTICIPANTS: One hundred thirty-six (272 eyes) were recruited from diabetic
retinopathy screening clinic of Royal Perth Hospital, Western Australia,
Australia. METHODS: All patients underwent three-field (optic disc, macular and
temporal view) mydriatic retinal digital still photography captured by EyeScan
and FF450 plus (Carl Zeiss Meditec, North America) and were subsequently examined
by a senior consultant ophthalmologist using the slit-lamp biomicroscopy
(reference standard). All retinal images were interpreted by a consultant
ophthalmologist and a medical officer. MAIN OUTCOME MEASURES: The sensitivity,
specificity and kappa statistics of EyeScan and FF450 plus with reference to the
slit-lamp examination findings by a senior consultant ophthalmologist. RESULTS:
For detection of any grade of diabetic retinopathy, EyeScan had a sensitivity and
specificity of 93 and 98%, respectively (ophthalmologist), and 92 and 95%,
respectively (medical officer). In contrast, FF450 plus images had a sensitivity
and specificity of 95 and 99%, respectively (ophthalmologist), and 92 and 96%,
respectively (medical officer). The overall kappa statistics for diabetic
retinopathy grading for EyeScan and FF450 plus were 0.93 and 0.95 for
ophthalmologist and 0.88 and 0.90 for medical officer, respectively. CONCLUSIONS:
Given that the EyeScan requires minimal training to use and has excellent
diagnostic accuracy in screening for diabetic retinopathy, it could be
potentially utilized by the primary eye care providers to widely screen for
diabetic retinopathy in the community.
PMID- 22044678
TI - Land trust evaluation of progress toward conservation goals.
AB - In the United States local land trusts preserve and conserve land to protect
water quality and supply, farmlands, habitat for native plants and animals, areas
of cultural or historical significance, and scenic views. We surveyed the 24
active, local land trusts in North Carolina (U.S.A.) to determine how they report
progress toward attaining such conservation goals. Twenty-two land trusts
responded to our survey. Of these, eight reported developing specific
conservation goals for all of the properties they protect, five identified
conservation targets on all properties, and two reported monitoring biological
indicators on all of their protected properties. On the basis of these results,
we believe most of the land trusts surveyed could not determine whether they were
meeting conservation goals because most did not identify explicit, measurable
goals and monitor progress toward them. Instead they reported success in terms of
the amount of land protected and money raised. We think this is a lost
opportunity for land trusts to build sound approaches to environmental
management, engage the public, entice new donors, and attain funding for
additional conservation activities. We propose conservation professionals help
local land trusts adopt the Open Standards for the Practice of Conservation, a
framework developed by a consortium of international conservation organizations,
to develop conservation goals and measure whether the goals are achieved.
PMID- 22044679
TI - Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by
Helicobacter pylori.
AB - Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize
humans. Gastric infections with this bacterium can induce pathology ranging from
chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori
isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and
HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a
type IV secretion system (T4SS). The adhesins establish tight bacterial contact
with host target cells and the T4SS represents a needle-like pilus device for the
delivery of effector proteins into host target cells such as CagA. BabA and SabA
bind to blood group antigen and sialylated proteins respectively, and a series of
T4SS components including CagI, CagL, CagY and CagA have been shown to target the
integrin beta1 receptor followed by injection of CagA across the host cell
membrane. The interaction of CagA with membrane-anchored phosphatidylserine may
also play a role in the delivery process. While substantial progress has been
made in our current understanding of many of the above factors, the host cell
receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we
review the recent progress in characterizing the interactions of the various
adhesins and structural T4SS proteins with host cell factors. The contribution of
these interactions to H. pylori colonization and pathogenesis is discussed.
PMID- 22044680
TI - Fighting resistant tuberculosis with old compounds: the carbapenem paradigm.
PMID- 22044681
TI - Service providers' perceptions of active ageing among older adults with lifelong
intellectual disabilities.
AB - BACKGROUND: Considerable attention is currently being directed towards both
active ageing and the revising of standards for disability services within
Australia and internationally. Yet, to date, no consideration appears to have
been given to ways to promote active ageing among older adults with intellectual
disabilities (IDs). METHODS: Semi-structured interviews were conducted with 16
Australian professional direct-care support staff (service providers) about their
perceptions of ageing among older adults with lifelong IDs and what active ageing
might entail for an individual from this population who is currently under their
care, in both the present and future. Data were analysed against the six core
World Health Organization active ageing outcomes for people with IDs. RESULTS:
Service providers appeared to be strongly focused on encouraging active ageing
among their clients. However, their perceptions of the individual
characteristics, circumstances and experiences of older adults with IDs for whom
they care suggest that active ageing principles need to be applied to this group
in a way that considers both their individual and diverse needs, particularly
with respect to them transitioning from day services, employment or voluntary
work to reduced activity, and finally to aged care facilities. The
appropriateness of this group being placed in nursing homes in old age was also
questioned. CONCLUSION: Direct-care staff of older adults with IDs have a vital
role to play in encouraging and facilitating active ageing, as well as informing
strategies that need to be implemented to ensure appropriate care for this
diverse group as they proceed to old age.
PMID- 22044682
TI - Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves
corneal integrity in the NOD model of Sjogren's syndrome.
AB - INTRODUCTION: In Sjogren's syndrome, keratoconjunctivitis sicca (dry eye) is
associated with infiltration of lacrimal glands by leukocytes and consequent
losses of tear-fluid production and the integrity of the ocular surface. We
investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR)
pathway on lacrimal-gland pathology in the NOD mouse model of Sjogren's syndrome.
METHODS: Male NOD mice were treated for up to ten weeks with an antagonist, LTBR
Ig, or control mouse antibody MOPC-21. Extra-orbital lacrimal glands were
analyzed by immunohistochemistry for high endothelial venules (HEV), by
Affymetrix gene-array analysis and real-time PCR for differential gene
expression, and by ELISA for CXCL13 protein. Leukocytes from lacrimal glands were
analyzed by flow-cytometry. Tear-fluid secretion-rates were measured and the
integrity of the ocular surface was scored using slit-lamp microscopy and
fluorescein isothiocyanate (FITC) staining. The chemokine CXCL13 was measured by
ELISA in sera from Sjogren's syndrome patients (n = 27) and healthy controls (n =
30). Statistical analysis was by the two-tailed, unpaired T-test, or the Mann
Whitney-test for ocular integrity scores. RESULTS: LTBR blockade for eight weeks
reduced B-cell accumulation (approximately 5-fold), eliminated HEV in lacrimal
glands, and reduced the entry rate of lymphocytes into lacrimal glands.
Affymetrix-chip analysis revealed numerous changes in mRNA expression due to LTBR
blockade, including reduction of homeostatic chemokine expression. The reduction
of CXCL13, CCL21, CCL19 mRNA and the HEV-associated gene GLYCAM-1 was confirmed
by PCR analysis. CXCL13 protein increased with disease progression in lacrimal
gland homogenates, but after LTBR blockade for 8 weeks, CXCL13 was reduced
approximately 6-fold to 8.4 pg/mg (+/- 2.7) from 51 pg/mg (+/-5.3) in lacrimal
glands of 16 week old control mice. Mice given LTBR blockade exhibited an
approximately two-fold greater tear-fluid secretion than control mice (P =
0.001), and had a significantly improved ocular surface integrity score (P =
0.005). The mean CXCL13 concentration in sera from Sjogren's patients (n = 27)
was 170 pg/ml, compared to 92.0 pg/ml for sera from (n = 30) healthy controls (P
= 0.01). CONCLUSIONS: Blockade of LTBR pathways may have therapeutic potential
for treatment of Sjogren's syndrome.
PMID- 22044683
TI - Age, gender, will, and use of home-visit nursing care are critical factors in
home care for malignant diseases; a retrospective study involving 346 patients in
Japan.
AB - BACKGROUND: We aimed to clarify the factors affecting outcomes of home care for
patients with malignant diseases. METHODS: Of 607 patients who were treated in 10
clinics specialized in home care between January and December 2007 at Chiba,
Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%;
145 men and 201 women) had malignant diseases. We collected information on
medical and social backgrounds, details of home care, and its outcomes based on
their medical records. RESULTS: Median age of the patients was 77 years (range,
11-102), and 335 patients were economically self-sufficient. Their general
condition was poor; advanced cancer (n = 308), performance status of 3-4 (n =
261), and dementia (n = 121). At the beginning of home care, 143 patients and 174
family members expressed their wish to die at home. All the patients received
supportive treatments including fluid replacement and oxygenation. Median
duration of home care was 47 days (range, 0-2,712). 224 patients died at home.
For the remaining 122, home care was terminated due to complications (n = 109),
change of attending physicians (n = 8), and others (n = 5). The factors which
inhibited the continuity of home care were the non-use of home-visit nursing care
(hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, p = 0.03),
the fact that the patients themselves do not wish to die at home (HR = 1.83, CI:
1.09-3.07, p = 0.02), women (HR = 1.81, CI: 1.11-2.94, p = 0.02), and age (HR =
0.98, CI: 0.97-1.00, p = 0.02). CONCLUSIONS: Continuation of home care is
influenced by patients' age, gender, will, and use of home-visit nursing.
PMID- 22044685
TI - Hydrolysis optimization and characterization study of preparing fatty acids from
Jatropha curcas seed oil.
AB - BACKGROUND: Fatty acids (FAs) are important as raw materials for the
biotechnology industry. Existing methods of FAs production are based on chemical
methods. In this study potassium hydroxide (KOH)-catalyzed reactions were
utilized to hydrolysis Jatropha curcas seed oil. RESULTS: The parameters effect
of ethanolic KOH concentration, reaction temperature, and reaction time to free
fatty acid (FFA%) were investigated using D-Optimal Design. Characterization of
the product has been studied using Fourier transforms infrared spectroscopy
(FTIR), gas chromatography (GC) and high performance liquid chromatography
(HPLC). The optimum conditions for maximum FFA% were achieved at 1.75M of
ethanolic KOH concentration, 65 degrees C of reaction temperature and 2.0 h of
reaction time. CONCLUSIONS: This study showed that ethanolic KOH concentration
was significant variable for J. curcas seed oil hydrolysis. In a 18-point
experimental design, FFA% of hydrolyzed J. curcas seed oil can be raised from
1.89% to 102.2%, which proved by FTIR and HPLC.
PMID- 22044686
TI - Extensive recombination events and horizontal gene transfer shaped the Legionella
pneumophila genomes.
AB - BACKGROUND: Legionella pneumophila is an intracellular pathogen of environmental
protozoa. When humans inhale contaminated aerosols this bacterium may cause a
severe pneumonia called Legionnaires' disease. Despite the abundance of dozens of
Legionella species in aquatic reservoirs, the vast majority of human disease is
caused by a single serogroup (Sg) of a single species, namely L. pneumophila Sg1.
To get further insights into genome dynamics and evolution of Sg1 strains, we
sequenced strains Lorraine and HL 0604 1035 (Sg1) and compared them to the
available sequences of Sg1 strains Paris, Lens, Corby and Philadelphia, resulting
in a comprehensive multigenome analysis. RESULTS: We show that L. pneumophila Sg1
has a highly conserved and syntenic core genome that comprises the many
eukaryotic like proteins and a conserved repertoire of over 200 Dot/Icm type IV
secreted substrates. However, recombination events and horizontal gene transfer
are frequent. In particular the analyses of the distribution of nucleotide
polymorphisms suggests that large chromosomal fragments of over 200 kbs are
exchanged between L. pneumophila strains and contribute to the genome dynamics in
the natural population. The many secretion systems present might be implicated in
exchange of these fragments by conjugal transfer. Plasmids also play a role in
genome diversification and are exchanged among strains and circulate between
different Legionella species. CONCLUSION: Horizontal gene transfer among bacteria
and from eukaryotes to L. pneumophila as well as recombination between strains
allows different clones to evolve into predominant disease clones and others to
replace them subsequently within relatively short periods of time.
PMID- 22044687
TI - Decreased xanthine oxidoreductase (XOR) is associated with a worse prognosis in
patients with serous ovarian carcinoma.
AB - OBJECTIVE: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of
DNA, RNA and high-energy phosphates. In the human cancers previously studied,
down-regulated XOR identifies patients with unfavorable prognosis. We assessed
the clinical relevance of XOR expression in serous ovarian cancer. METHODS: XOR
protein was determined in tissue microarrays from 474 patients with serous
ovarian cancer and analyzed with respect to clinical parameters and survival.
RESULTS: XOR was down regulated in 64% of the tumors as compared to the
corresponding normal tissue. Decreased XOR was associated with a poorly
differentiated tumor and an abnormal p53 expression, but not with age at
diagnosis, FIGO stage, Ki-67 or tumor size. XOR expression was associated with
outcome, and the five year ovarian cancer specific survival in patients with
strong XOR expression was 59% compared to 44% in those with moderate (hazard
ratio, HR; 1.44; P=0.0083) and 26% in patients with lack of XOR (HR, 2.07;
P=0.0003). This was also true in patients whose tumors were highly differentiated
(HR, 3.67; P=0.008) and in patients with a small (<1cm) residual tumor (HR, 2.62;
P=0.017), and in patients whose tumors show a low Ki-67 protein expression (HR,
3.79; P<0.0001). In multivariate survival analysis, absence of XOR emerged as an
independent prognostic factor (HR, 1.82; P=0.015). CONCLUSIONS: Decreased XOR is
associated with poorer prognosis in patients with serous ovarian cancer
especially in those with an otherwise more favorable prognostic profile.
PMID- 22044688
TI - Involvement in decision-making about treatment and ovarian cancer survivor
quality of life.
AB - PURPOSE: This study sought to better understand the long-term effects on women's
health related quality of life (HRQOL) of involvement in decision-making about
their surgical and chemotherapeutic treatments for ovarian cancer treatment and
about follow-up care after treatment. METHODS: Using a cross-sectional survey
design, a sample of 219 ovarian cancer patient/survivors from Western Washington
who were between 3 months and ten years post-diagnosis were recruited via a
mailed survey sent by their gynecological oncologist and interviewed about their
ovarian cancer treatment, use of Complementary and Alternative Medicine (CAM),
Health related quality of life, and their involvement in decision-making about
their cancer treatment and follow-up care. RESULTS: Multivariate regression
analyses revealed age, but not stage of cancer to be a significant predictor of
perceived involvement in decision-making about ovarian cancer treatment and
follow-up. Age also predicted CAM use with older patients using herbal CAM, and
younger patients using CAM activities and CAM providers (p<0.5). Controlling for
demographic, disease, and treatment characteristics involvement in decision
making about surgery and follow-up care were associated with better mental health
in survivorship (p<0.05). Involvement in decision-making about use of CAM and
about lifestyle health changes was associated with greater vitality and better
role-emotional health in survivorship (respectively; both; p<0.05). CONCLUSIONS:
As has been found in studies of breast cancer survivors, perceived involvement in
decision-making about ovarian cancer treatment including surgery and follow-up
care after treatment is associated with better quality of life for cancer
survivors. Involvement in decision-making about the use of CAM and about changes
in lifestyle health practices also appear to help survivor's emotional health
related quality of life. Prospective studies are needed to determine the
mechanisms by which perceived involvement in decision-making about treatment
might influence survivor quality of life.
PMID- 22044689
TI - BRCA1 and BRCA2 mutations among ovarian cancer patients from Colombia.
AB - OBJECTIVE: The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in
Colombia has not yet been explored. Five founder mutations have been identified
in two previous studies of breast cancer patients in the Bogota region [1,2]. It
is important that the frequency of mutations be established among unselected
cases of ovarian cancer in order to estimate the genetic burden of this cancer in
Colombia and to plan genetic and preventive services. METHODS: We enrolled 100
unselected women with ovarian cancer from the Bogota region, and from northern
and southern central regions of Colombia. A detailed family history was obtained
from each patient and a blood sample was processed for DNA analysis. DNA quality
was adequate for BRCA testing for 96 women. Mutations in BRCA1 and BRCA2 were
sought using a Hispanic BRCA mutation testing panel. All mutations were confirmed
by direct sequencing. RESULTS: Fifteen mutations were identified (two in BRCA2
and thirteen in BRCA1) representing 15.6% of the total (95% CI: 7.8% to 21.3%).
Among the 15 mutation-positive families there were nine breast-ovarian cancer
families, one gastric cancer family, one prostate cancer family, three uterine
cancer families, and one family with no history of cancer. A single founder
mutation in BRCA1 (3450del4) was seen in 11 patients. CONCLUSION: In summary,
BRCA1 founder mutations are common in Colombian women with ovarian cancer.
Approximately 11.5% of all ovarian cancer cases in the Bogota region are
attributable to a single BRCA1 founder mutation.
PMID- 22044690
TI - Characterization of hTERT-immortalized caprine mammary epithelial cells.
AB - The aim of this article is to demonstrate and characterize caprine mammary
epithelial cells (CMC) immortalized with human telomerase reverse transcriptase
(hTERT) gene. Five immortalized CMCs were assigned to either myoepithelial or
luminal epithelial groups based on their morphology and expression of cell
lineage-specific intermediate filaments. Telomeric repeat amplification protocol
revealed various telomerase activities in CMCs associated with their distinct
proliferation potential. Karyotypic analysis showed three CMCs retained their
modal Capra hircus chromosome number (2n = 60), whereas the remaining two CMCs
were abnormal at 2n = 19 and 2n = 36. CMCs with abnormal karyotypes lost p53
protein after chemical-induced DNA damage and showed anchorage-independent growth
in soft agar assay. In terms of functional differentiation, luminal CMCs
organized into alveolus-like structures when grown in Matrigel. Furthermore,
alphas1- and beta-casein gene was induced in luminal CMCs in response to lacto
hormones stimulation. Together these results showed that hTERT-immortalized CMCs
retained major characteristics of mammary epithelial cells, and stability of the
genome is required for maintaining normal mammary epithelium function.
Application of CMCs can provide valuable models to study alveologenesis and
lactogenesis of mammary epithelium and test the feasibility of recombinant
constructs designed for the generation of transgenic livestock.
PMID- 22044692
TI - Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII
in experimental haemophilia A.
AB - The development of inhibitory anti-factor VIII (FVIII) antibodies in patients
with haemophilia A following replacement therapy is associated with several types
of risk factors. Among these, the purity of FVIII concentrates, and in particular
the presence of von Willebrand factor (VWF), was controversially proposed to
influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in
vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective
effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia
A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic
cells and evaluated the capacity of VWF to block the internalization of FVIII. We
characterized the relevance of VWF for the accumulation of FVIII in the marginal
zone of the spleen, a secondary lymphoid organ where the immune response to
therapeutically administered FVIII initiates. Our results confirm that VWF
reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF
is important for the accumulation of FVIII in the marginal zone of the spleen. We
propose that VWF exerts at least two non-mutually exclusive immunoprotective
roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by
professional antigen-presenting cells by blocking the interaction of FVIII with
as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of
increasing the half-life of FVIII in the circulation, may allow an increased
contact time with tolerogenic marginal zone B cells in the spleen.
PMID- 22044691
TI - Protein expression, survival and docetaxel benefit in node-positive breast cancer
treated with adjuvant chemotherapy in the FNCLCC-PACS 01 randomized trial.
AB - INTRODUCTION: The PACS01 trial has demonstrated that a docetaxel addition to
adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS)
and overall survival of node-positive early breast cancer (EBC). We searched for
prognostic and predictive markers for docetaxel's benefit. METHODS: Tumor samples
from 1,099 recruited women were analyzed for the expression of 34 selected
proteins using immunohistochemistry. The prognostic and predictive values of each
marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing,
and triple-negative) were tested. RESULTS: Progesterone receptor-negativity (HR =
0.66; 95% CI 0.47 to 0.92, P = 0.013), and Ki67-positivity (HR = 1.53; 95% CI
1.12 to 2.08, P = 0.007) were independent adverse prognostic factors. Out of the
34 proteins, only Ki67-positivity was associated with DFS improvement with
docetaxel addition (adjusted HR = 0.51, 95% CI 0.33 to 0.79 for Ki67-positive
versus HR = 1.10, 95% CI 0.75 to 1.61 for Ki67-negative tumors, P for interaction
= 0.012). Molecular subtyping predicted the docetaxel benefit, but without
providing additional information to Ki67 status. The luminal A subtype did not
benefit from docetaxel (HR = 1.16, 95% CI 0.73 to 1.84); the reduction in the
relapse risk was 53% (HR = 0.47, 95% CI 0.22 to 1.01), 34% (HR = 0.66, 95% CI
0.37 to 1.19), and 12% (HR = 0.88, 95% CI 0.49 to 1.57) in the luminal B, HER2
overexpressing, and triple-negative subtypes, respectively. CONCLUSIONS: In
patients with node-positive EBC receiving adjuvant anthracycline-based
chemotherapy, the most powerful predictor of docetaxel benefit is Ki67
positivity.
PMID- 22044693
TI - Hepatic transplant and HCV: a new playground for an old virus.
AB - Hepatitis C virus (HCV) infection is a major global health problem affecting 170
million people worldwide. The majority of infected individuals fail to resolve
their infection, with a significant number developing chronic, progressive HCV
related liver disease. HCV infection is the leading indication for liver
transplantation and unfortunately, all patients with detectable viral load before
transplantation will have rapid, recurrent infection. What remain to be
determined are factors contributing to the severity of HCV recurrence. Such
factors are unique to the posttransplant setting and include: viral genetic
diversity and composition, immunosuppression, donor/recipient age and sex,
genetic factors and the liver microenvironment. Importantly, the possibility that
the severity of HCV recurrence might be also influenced by factors related to the
primary course of disease (i.e. viral set point, previously acquired adaptations
of the virus) must be further evaluated. In this sense, recurrent HCV infection
should not be regarded merely as another acute infection, but rather, it should
be cautioned that problems first arising during the primary course of disease may
be accentuated during recurrence. Development of novel therapeutic approaches
will require a thorough understanding of viral and host determinants of infection
resolution and how these factors may change in the posttransplant setting.
PMID- 22044694
TI - Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate
cancer patients before prostatectomy: evaluation of potential chemopreventive
activities.
AB - Compelling preclinical and pilot clinical data support the role of green tea
polyphenols in prostate cancer prevention. We conducted a randomized, double
blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol
extract) in men with prostate cancer scheduled to undergo radical prostatectomy.
The study aimed to determine the bioavailability of green tea polyphenols in
prostate tissue and to measure its effects on systemic and tissue biomarkers of
prostate cancer carcinogenesis. Participants received either polyphenon E
(containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks
before surgery. Following the intervention, green tea polyphenol levels in the
prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted
in favorable but not statistically significant changes in serum prostate-specific
antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood
leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis
in the prostatectomy tissue did not differ between the treatment arms. The
proportion of subjects who had a decrease in Gleason score between biopsy and
surgical specimens was greater in those on polyphenon E but was not statistically
significant. The study's findings of low bioavailability and/or bioaccumulation
of green tea polyphenols in prostate tissue and statistically insignificant
changes in systemic and tissue biomarkers from 3 to 6 weeks of administration
suggests that prostate cancer preventive activity of green tea polyphenols, if
occurring, may be through indirect means and/or that the activity may need to be
evaluated with longer intervention durations, repeated dosing, or in patients at
earlier stages of the disease.
PMID- 22044696
TI - Suppressor of cytokine signal 3 and IL28 genetic variation predict the viral
response to peginterferon and ribavirin.
AB - AIM: The aim of this study was to investigate the relationship among the
expression of suppressor of cytokine signaling 3 (SOCS 3) in the liver, the SNPs
in the IL28B locus, and the outcome of interferon therapy. METHODS: Prior to
interferon treatment, we immunostained 67 liver specimens from chronic hepatitis
C (CHC) patients who were receiving peginterferon alpha-2b/ribavirin therapy for
suppressor of cytokine signaling 3 (SOCS3), and compared the expression of SOCS3,
IL28 polymorphisms and other clinical factors between the patients and compared
their eventual outcomes. RESULTS: Significant differences between the low SOCS3
group and high SOCS3 group were found in age, as well as in the platelet,
transaminase, gamma-glutamyl transpeptidase levels. The incidence of high SOCS3
was not significantly different between subjects with the TT genotype and the TG
genotype (TT : TG = 71%:29%, P = 0.250). In a multivariate analysis, age (>=65
years old) (odds ratio 0.221 [0.120-0.966], P = 0.045), IL28B gene (genotype TT)
(odds ratio 5.422 [1.254-23.617], P = 0.024) and SOCS3 (high) (odds ratio 0.308
[0.104-0.948], P = 0.040) were significant predictors of the interferon response.
In patients with the TT genotype, those with low SOCS3 immunostaining showed a
high sustained virological response (69%), while the sustained virological rate
was low (27%) in the patients with high SOCS3 immunostaining. CONCLUSIONS:
Using a combination of the SOCS3 immunostained area in the liver and the
expression of IL28B single nucleotide polymorphisms might be a useful predictor
of hepatitis C virus clearance by interferon therapy.
PMID- 22044695
TI - Genetic variants associated with the risk of chronic obstructive pulmonary
disease with and without lung cancer.
AB - Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung
cancer. Published studies about variations of genes encoding glutathione
metabolism, DNA repair, and inflammatory response pathways in susceptibility to
COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP)
from 56 genes of these three pathways in 620 cases and 893 controls to identify
susceptibility markers for COPD risk, using existing resources. We assessed SNP-
and gene-level effects adjusting for sex, age, and smoking status. Differential
genetic effects on disease risk with and without lung cancer were also assessed;
cumulative risk models were established. Twenty-one SNPs were found to be
significantly associated with risk of COPD (P < 0.01); gene-based analyses
confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2,
ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold;
eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered
the risk with lung cancer by 2.3-fold. Our findings indicate that multiple
genetic variations in the three selected pathways contribute to COPD risk through
GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to
elucidate the mechanisms of these genes in the development of COPD, lung cancer,
or both.
PMID- 22044697
TI - Morphologic outer retinal abnormalities in white dot syndromes on spectral-domain
optical coherence tomography.
PMID- 22044699
TI - Real time triplane echocardiography in the assessment of the functional area of
prosthetic aortic valves: reliability and feasibility.
AB - PURPOSE: Our study is aimed at evaluating the feasibility and reliability of a
simple method for the measurement of the functional area of prosthetic aortic
valves (EOA). Three-dimensional echocardiography has proven accurate for left
ventricular volume, stroke volume, and aortic valve area measurement. We studied
the feasibility and reliability of real time simultaneous triplane
echocardiography (RT3P) for assessing the EOA with a fast formula based on the
principle of continuity equation, in which we replaced Doppler-derived stroke
volume (SV) with SV directly measured with RT3P. METHODS AND RESULTS: EOA of
prosthetic aortic valves were measured in 23 consecutive patients requiring
periodical follow up. EOA was calculated using Doppler continuity equation (DCE)
and the RT3P method by replacing Doppler-derived SV with SV measured with real
time triplane echocardiography. We compared functional areas obtained with the
two methods with the prosthetic area indicated in the manufacturer's
specifications and with the mean transprosthetic gradient. Both methods had a
good correlation with the area indicated by the manufacturer. RT3P revealed an
inverse correlation between functional area and mean gradient that was better
than DCE (P = 0.0359). Inter- and intraobserver variability was not different
between the two methods. Execution time was significantly shorter for RT3P.
CONCLUSIONS: RT3P is a simple method that can be performed quite rapidly, and can
complement the overall assessment of prosthetic valve function. Further studies
can confirm our technique.
PMID- 22044700
TI - How can benfluorex-related heart valve disease be identified by echocardiography?
PMID- 22044698
TI - "Targeted disruption of the epithelial-barrier by Helicobacter pylori".
AB - Helicobacter pylori colonizes the human gastric epithelium and induces chronic
gastritis, which can lead to gastric cancer. Through cell-cell contacts the
gastric epithelium forms a barrier to protect underlying tissue from pathogenic
bacteria; however, H. pylori have evolved numerous strategies to perturb the
integrity of the gastric barrier. In this review, we summarize recent research
into the mechanisms through which H. pylori disrupts intercellular junctions and
disrupts the gastric epithelial barrier.
PMID- 22044701
TI - A cross-sectional evaluation of venous thromboembolism risk and use of venous
thromboembolism prophylaxis in hospitalized patients in Senegal.
AB - BACKGROUND: Venous thromboembolism is a common and preventable cause of morbidity
and mortality in hospitalized patients. There is a lack of data on the
distribution of risk factors and prophylaxis practices in sub-Saharan Africa.
AIM: To assess the prevalence of venous thromboembolism risk in hospitalized
patients and to determine the proportion of at-risk patients who receive
prophylaxis. METHODS: The study was a cross-sectional hospital-based survey. On
the basis of the global ENDORSE methodology, patients aged>=40 years admitted to
a medical ward or those aged>=18 years admitted to a surgical ward were assessed
for risk of venous thromboembolism by hospital chart review. Distribution of risk
factors and coverage of prophylaxis in at-risk patients were determined using the
2004 American College of Chest Physicians evidence-based consensus guidelines.
RESULTS: From October to November 2008, 520 patients (278 medical; 242 surgical)
were enrolled in 12 hospitals across Senegal. Two hundred and ninety-eight (57%)
were at risk of venous thromboembolism; 152 (57.4%) medical patients and 146
(60.3%) surgical patients. Among those at risk, 48 (31.6%) medical patients and
52 (35.6%) surgical patients received a prescription for prophylaxis. Among
patients without contraindication to anticoagulants, 33.8% (46/136) on medical
wards and 37.5% (48/128) on surgical wards received prophylaxis. CONCLUSION: The
risk of venous thromboembolism was frequent in hospitalized patients in Senegal
but only a few received the recommended prophylaxis. There is a need to implement
a programme to improve venous thromboembolism awareness and prophylaxis.
PMID- 22044702
TI - Usefulness of serum albumin and serum total cholesterol in the prediction of
hospital death in older patients with severe, acute heart failure.
AB - BACKGROUND: Acute heart failure (HF) carries high hospital mortality rates in
older patients; a multimarker strategy may help identify patients at high risk.
AIMS: To investigate prospectively the prognostic relevance of serum albumin and
serum total cholesterol (TC) in older patients with severe, acute HF. METHODS:
Usual prognostic variables were collected on admission in 207 consecutive
patients aged>70 years with severe, acute HF. Serum albumin and serum TC were
obtained soon after clinical improvement. RESULTS: Hospital mortality rate was
19%. Patients who died were similar to patients who survived in terms of age,
sex, heart rate, serum haemoglobin and left ventricular ejection fraction.
Patients who died had higher concentrations of B-type natriuretic peptide (BNP),
blood urea nitrogen, serum creatinine, C-reactive protein and serum troponin I,
lower systolic blood pressure, and lower concentrations of serum albumin and
serum TC than patients who survived (P<0.01 for all). Serum albumin was the best
independent predictor of hospital death (odds ratio 0.82 [0.74-0.90], P<0.001),
with blood urea nitrogen (P=0.02) and log (BNP) (P=0.02). A simple risk score
based on serum albumin (<3g/dL; 2 points), BNP (>840pg/mL; 1 point) and blood
urea nitrogen (>15.3mmol/L; 1 point) discriminated patients without (score 0 to
1, hospital death 4%) from patients with (score 2 to 4, hospital death 35%,
P<0.001) a high risk of death. CONCLUSION: Hypoalbuminaemia offers powerful
additional prognostic information to usual prognostic variables in older patients
with severe, acute HF, and deserves further attention in multimarker strategies.
PMID- 22044703
TI - Evolution of acute coronary syndrome with normal coronary arteries and normal
cardiac magnetic resonance imaging.
AB - BACKGROUND: Acute coronary syndrome (ACS) with normal coronary angiography is a
frequent clinical situation with an uncertain prognosis. Cardiac magnetic
resonance imaging (CMRI) is a powerful tool for differential diagnosis between
myocardial infarction (MI), acute myocarditis and Tako-tsubo cardiomyopathy
(TTC). Data are sparse regarding the evolution of patients presenting an ACS with
normal coronary arteries and normal CMRI. AIMS: To evaluate the evolution of
patients presenting an ACS with normal coronary arteries and normal CMRI, with a
1-year follow-up. METHODS: Eighty-seven consecutive patients (mean age, 53 years;
40.2% men) presenting an ACS with troponin elevation and normal coronary arteries
by angiography were prospectively included. All patients underwent CMRI at 3
Tesla. Adverse events were recorded with 1-year follow-up. RESULTS: A likely
aetiology for the acute clinical presentation was established by CMRI in 63.2% of
patients (22.7% MI, 26.4% acute myocarditis, 11.5% TTC). During follow-up, one
patient in the MI group had a stroke (1.2%). In the myocarditis group, there was
one initial cardiogenic shock, one episode of congestive heart failure (1.2%) and
nine patients had recurrent chest pain without troponin elevation (10.3%). Two
TTC group patients initially presented with cardiogenic shock (2.4%); there were
no other adverse events in this group during follow-up. In the remaining 36.7%
patients, no clear diagnosis could be identified by CMRI, and no adverse events
occurred during follow-up. CONCLUSION: CMRI is a useful tool for the management
of ACS presenting with normal coronary angiography, as it helps to ascertain the
diagnosis and adapt treatment in a large proportion of cases. Nonetheless,
patients with no abnormalities identified by CMRI have an excellent evolution.
PMID- 22044704
TI - Vascular function and mortality in haemodialysis patients: a pilot study.
AB - BACKGROUND: Haemodialysis patients often have impaired vascular function that can
contribute to mortality. Endothelial-dependent and -independent vascular function
can be assessed using the brachial artery reactivity (BAR) technique that
measures flow-mediated dilatation (FMD) and the response to glyceryl trinitrate
(GTN), respectively. AIMS: The aim of this pilot study was to determine whether
BAR measurements in haemodialysis patients were associated with mortality.
METHODS: Brachial artery responses to FMD and administration of GTN were assessed
in consecutive haemodialysis patients. Patients were then followed up to 18
months after BAR measurements. RESULTS: Seventeen patients were included in the
study. After 18 months of follow-up, patients were divided into two groups:
survived (n=12) and deceased (n=5). Patients who survived had a significantly
greater median percentage vasodilatation to GTN than those who died (19.1% vs
8.8%; P=0.04); and a significantly greater median area under the diameter change
time curve (318 vs 146 mm/s; P=0.03). However, there were no significant
differences between survivors and deceased in median percentage vasodilation to
FMD (6.0% vs 4.3%; P=0.21), time to peak dilation (45 vs 40s; P=0.66) or area
under the diameter change-time curve (35.5 vs 20 mm/s; P=0.29). CONCLUSION: In
this pilot study in a small group of haemodialysis patients, endothelial
independent vasodilatory response to GTN was associated with mortality and was of
better prognostic value than the endothelial-dependent response to FMD. This
finding needs to be investigated in a larger cohort.
PMID- 22044705
TI - Diagnostic accuracy of quantitative heart-fatty acid binding protein assays
compared with Cardiodetect((r)) in the early detection of acute coronary
syndrome.
AB - BACKGROUND: Heart-fatty acid binding protein (h-FABP) has been proposed as a
cardiac marker for the early detection of acute coronary syndrome (ACS). In a
study of 677 patients admitted to the emergency department (ED) for chest pain,
we found that a semiquantitative point-of-care test that detects h-FABP
(Cardiodetect((r))) had low sensitivity for the prediction of ACS. OBJECTIVE: The
aim of this ancillary study was to analyze and compare the performance of h-FABP
for early ACS diagnosis in this large cohort of unselected patients, using a
quantitative immunoassay and Cardiodetect((r)). METHODS: h-FABP was measured with
a ready-to-use, solid-phase, enzyme-linked immunosorbent assay (ELISA) in 677
patients admitted to the ED with chest pain and suspected non-ST-segment
elevation ACS. Two physicians, blinded to the results of the marker, categorized
patients as having or not having non-ST-segment elevation ACS. RESULTS: Non-ST
segment elevation ACS was diagnosed in 185 patients (27.3%). The median h-FABP
level was higher in patients with ACS (1.36MUg/L, interquartile range [IQR] 0.59
3.55) than in those without ACS (0.58MUg/L, IQR 0.24-1.34; P<0.01). The area
under the curve was 0.68 (95% confidence interval [CI] 0.63-0.73). h-FABP did not
improve the performance of a model that included the usual diagnostic tools for
ACS management (odds ratio 0.92, 95% CI 0.32-2.70). The classification agreement
between the ELISA and Cardiodetect((r)) was 92.1% (kappa 0.39). CONCLUSION: In
this study, we confirmed that measurement of h-FABP was insufficient to be used
as a marker of ACS and NSTEMI in ED, whatever the analytical technique used.
PMID- 22044706
TI - Characteristics of isolated atrial flutter versus atrial flutter combined with
atrial fibrillation.
AB - BACKGROUND: Atrial flutter (AFL) and atrial fibrillation (AF) are "fellow
travellers". AF may be a stable, "isolated" rhythm, a bridge between sinus rhythm
and AF, or both arrhythmias can coexist. Whether the characteristics of isolated
AFL are different from those of patients with AFL combined with AF is still
unclear. AIM: To compare the clinical characteristics of patients with isolated
AFL to those of patients with AFL combined with AF, in a series of patients
referred for AFL ablation. METHODS: Seventy-six consecutive patients (mean age
66.9+/-12.2 years; 53 men) with a history of electrocardiogram-documented
paroxysmal or persistent AFL, referred for catheter ablation, underwent clinical
work-up including bidimensional echocardiogram. Patients were subdivided into
group I (44 with isolated AFL) and group II (32 with AFL and a history of AF).
RESULTS: Underlying heart disease was present in 62 patients (81.6%).
Hypertension was the most common cardiac disorder (n=44, 57.9%) and was more
prevalent in group II than in group I (75.0% vs 45.5%; P=0.01). Prevalence of
prior cardiac surgery was higher in group I (22.7% vs 6.3%; P=0.04). AFL was
persistent in 35 group I patients and 17 group II patients (79.5% vs 53.1%;
P=0.01). Class I or III antiarrhythmic drug use was more frequent in group II
(84.4% vs 45.5%; P=0.001). CONCLUSION: This study showed significant differences
between patients with isolated AFL and those with AFL combined with AF, in the
prevalence of underlying heart disease and the use of antiarrhythmic medication,
which were higher when both atrial arrhythmias were combined. In turn, the
history of cardiac surgery (including atriotomy), was more common in patients
with isolated AFL than in those with AFL combined with AF.
PMID- 22044707
TI - Update on the medical treatment of stable angina.
AB - Stable angina is a form of coronary artery disease. Its potential to progress
requires the most appropriate treatment in order to reduce the incapacitating
effect of an acute angina attack and to avoid long-term cardiovascular events.
With or without revascularization, pharmacological treatment is an essential
component of this treatment strategy, which also involves lifestyle and diet.
Statins and aspirin have been shown to be effective in preventing different
aspects of coronary artery disease overall. The efficacy of other classes of
treatment has been demonstrated in contexts such as stable angina (including
postmyocardial infarction) and heart failure (under specific conditions of
dosing) for beta-blockers and in contexts such as heart failure, postinfarction
and following revascularization for angiotensin-converting enzyme inhibitors.
Along with the oldest classes of treatment, such as nitrates (and related
derivatives), beta-blockers and calcium channel blockers, new classes of
treatments with entirely (trimetazidine, ivabradine) or partly (nicorandil)
different mechanisms of action have now been added. The latest antianginal to
obtain marketing authorization, ranolazine, is not yet available in France. The
different levels of evidence of the efficacy of these pharmacological products
vary greatly and overall are higher for those developed most recently. None is
devoid of side effects, which must be taken into account in these patients, many
of whom are elderly and polymedicated.
PMID- 22044708
TI - An unusual cause of systolic murmur.
PMID- 22044709
TI - Use of umbilical venous catheter before performing Rashkind's procedure.
PMID- 22044710
TI - Unusual monocoronary system and sudden death.
PMID- 22044711
TI - Incidentally found double-orifice mitral valve in an elderly patient.
PMID- 22044712
TI - Police encounters with people with intellectual disability: prevalence,
characteristics and challenges.
AB - BACKGROUND: This study investigated the experiences and perceptions of
operational members of Victoria Police in relation to their contacts with people
with intellectual disability (ID). Key interests for exploration included how
frequently and in what context police reported coming into contact with people
with ID, how they made this identification, and the challenges they experienced
at this interface. METHODS: Participants comprised 229 operational police members
who attended mandatory firearms training sessions over a 2-week period in
Melbourne, Australia. RESULTS: Police reported coming into contact with people
they believed to have an ID on a regular basis and for a wide variety of reasons.
They were most likely to base their knowledge on job-related experiences and were
most likely to identify individuals on the basis of physical and behavioural
cues. The most common challenges were communication, and gaining access to
assistance and co-operation from other service providers. While many considered
themselves capable in their interactions with those with ID, those who identified
that they were most in need of training reported lower confidence in how to
respond in these encounters. CONCLUSIONS: Future training needs to focus on
differentiating between mental illness and ID, techniques for enhancing
identification and communication, and the inclusion of hands-on scenario-based
sessions involving an interdisciplinary approach.
PMID- 22044713
TI - Examining the stable door after the horse has bolted: why is EIA such a
challenge?
PMID- 22044714
TI - Immunological differences in the global release of the major cat allergen Fel d 1
are influenced by sex and behaviour.
AB - The biological function of Fel d 1, the major cat allergen released in the
environment, is still unclear despite studies suggesting a putative role in
chemical communication. Structural and immunological polymorphisms of Fel d 1
have been described. This study examined how Fel d 1 immunological polymorphism
may have a physiological origin by estimating a potential relationship with the
sex of cats and cat-human interactions. Samples from bath washes of 21 cats were
screened to study antibody binding to Fel d 1 using an ELISA. Personality and
Tolerance Handling scores were used to assess the behaviour of the cats. In the
washes, Fel d 1 concentrations were significantly lower in females than in males
(P<0.05). Slopes from the ELISA dose-dependent curves varied among the cats:
males secreted Fel d 1 variants with higher antibody recognition than females
(P<0.01). Females that were aggressive and difficult to handle displayed a
diminished slope value, and therefore a weaker Fel d 1 immunoreactivity in global
washes, compared to females that were sociable (P=0.09) and easy to handle
(P=0.07). This study shows a variable immunological polymorphism of Fel d 1
within a cat population, particularly between males and females, and this
polymorphism appears to be related to cat-human interactions.
PMID- 22044715
TI - The developmental sequence of tobacco withdrawal symptoms of wanting, craving and
needing.
AB - OBJECTIVE: The first case series on tobacco addiction suggested that withdrawal
symptoms evolve through a clear developmental sequence both over the clinical
course and during an episode of abstinence. The objective of the current study
was to determine if this observation would be confirmed by a second case series.
METHODS: The subjects were 25 adolescent and adult smokers. Subjects were
provided with operational definitions of the withdrawal symptoms of wanting,
craving and needing. Using nondirective techniques, detailed histories of
subjects' experiences with these three symptoms during abstinence from tobacco
were obtained in individual interviews. RESULTS: All 25 subjects identified the
operational definitions of wanting and craving as symptoms they had experienced,
and 21 subjects indicated that the definition of needing described a symptom they
had experienced. All 25 subjects reported that wanting was the first symptom they
had experienced; 24 of 25 subjects reported that craving was the second symptom
experienced; and 20 of the 21 subjects that had experienced needing reported that
this was the third symptom they had experienced. All subjects reported that
during abstinence symptoms appeared in the order of wanting, craving and needing.
Subjects reported that stress-induced urges to smoke are not relieved by smoking,
do not follow a characteristic sequence, and do not have a latency. CONCLUSIONS:
Abstinence from tobacco provokes characteristic symptoms of wanting, craving and
needing that are widely endorsed by smokers as symptoms they have experienced.
These symptoms develop in a set sequence of wanting, craving and needing in all,
or nearly all, smokers over their clinical course. These symptoms recur in the
same sequence during acute episodes of abstinence. Smokers can distinguish
between four symptoms: wanting, craving, needing and stress-induced urges to
smoke, but these distinctions are not captured by generic 'craving' measures.
PMID- 22044716
TI - Assessment of risk factors related to healthcare-associated methicillin-resistant
Staphylococcus aureus infection at patient admission to an intensive care unit in
Japan.
AB - BACKGROUND: Healthcare-associated methicillin-resistant Staphylococcus aureus (HA
MRSA) infection in intensive care unit (ICU) patients prolongs ICU stay and
causes high mortality. Predicting HA-MRSA infection on admission can strengthen
precautions against MRSA transmission. This study aimed to clarify the risk
factors for HA-MRSA infection in an ICU from data obtained within 24 hours of
patient ICU admission. METHODS: We prospectively studied HA-MRSA infection in 474
consecutive patients admitted for more than 2 days to our medical, surgical, and
trauma ICU in a tertiary referral hospital in Japan. Data obtained from patients
within 24 hours of ICU admission on 11 prognostic variables possibly related to
outcome were evaluated to predict infection risk in the early phase of ICU stay.
Stepwise multivariate logistic regression analysis was used to identify
independent risk factors for HA-MRSA infection. RESULTS: Thirty patients (6.3%)
had MRSA infection, and 444 patients (93.7%) were infection-free. Intubation,
existence of open wound, treatment with antibiotics, and steroid administration,
all occurring within 24 hours of ICU admission, were detected as independent
prognostic indicators. Patients with intubation or open wound comprised 96.7% of
MRSA-infected patients but only 57.4% of all patients admitted. CONCLUSIONS: Four
prognostic variables were found to be risk factors for HA-MRSA infection in ICU:
intubation, open wound, treatment with antibiotics, and steroid administration,
all occurring within 24 hours of ICU admission. Preemptive infection control in
patients with these risk factors might effectively decrease HA-MRSA infection.
PMID- 22044717
TI - Initial survival data of kidney transplant patients with pre-transplant
monoclonal gammopathy.
AB - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is the
presence of a serum monoclonal protein at a concentration of <3 g/dL without
evidence of lymphoproliferative disease or organ damage. The prevalence of MGUS
in kidney transplantation (KT) candidates is unknown. The present is a
retrospective report of patients who underwent evaluation for a KT and were found
to have MGUS at our center. METHODS: All transplant candidates found to have MGUS
between the years 2000 and 2007 were included. Variables were collected. Patients
with MGUS that received a KT were compared with patients with MGUS that were not
transplanted. RESULTS: Of a total of 1215 KT candidates, 34 were found to have
MGUS during the KT evaluation. Nine patients with MGUS were transplanted. Myeloma
or lymphoproliferative disease was not observed. Following transplantation, the
MGUS group had a lower survival than the non-transplanted group. However,
survival from the time of MGUS diagnosis was not different between the
transplanted and non-transplanted MGUS groups. CONCLUSIONS: In this group,
transplantation did not confer a survival benefit. It is our hope that these
initial data will serve as a platform for future studies. We suggest MGUS
screening in all patients older than 50 yr of age undergoing evaluation for
transplantation.
PMID- 22044718
TI - Antibacterial activities of selected Cameroonian spices and their synergistic
effects with antibiotics against multidrug-resistant phenotypes.
AB - BACKGROUND: The emergence of multi-drug resistant (MDR) phenotypes is a major
public health problem today in the treatment of bacterial infections. The present
study was designed to evaluate the antibacterial activities of the methanol
extracts of eleven Cameroonian spices on a panel of twenty nine Gram negative
bacteria including MDR strains. METHODS: The phytochemical analysis of the
extracts was carried out by standard tests meanwhile the liquid micro-broth
dilution was used for all antimicrobial assays. RESULTS: Phytochemical analysis
showed the presence of alkaloids, phenols and tannins in all plants extracts. The
results of the antibacterial assays indicated that all tested extracts exert
antibacterial activities, with the minimum inhibitory concentration (MIC) values
varying from 32 to 1024 MUg/ml. The extracts from Dichrostachys glomerata,
Beilschmiedia cinnamomea, Aframomum citratum, Piper capense, Echinops giganteus,
Fagara xanthoxyloides and Olax subscorpioidea were the most active. In the
presence of efflux pump inhibitor, PAbetaN, the activity of the extract from D.
glomerata significantly increased on 69.2% of the tested MDR bacteria. At MIC/5,
synergistic effects were noted with the extract of D. glomerata on 75% of the
tested bacteria for chloramphenicol (CHL), tetracycline (TET) and norfloxacin
(NOR). With B. cinnamomea synergy were observed on 62.5% of the studied MDR
bacteria with CHL, cefepime (FEP), NOR and ciprofloxacin (CIP) and 75% with
erythromycin (ERY). CONCLUSION: The overall results provide information for the
possible use of the studied extracts of the spices in the control of bacterial
infections involving MDR phenotypes.
PMID- 22044719
TI - Peripheral regulation by ecdysteroids of olfactory responsiveness in male
Egyptian cotton leaf worms, Spodoptera littoralis.
AB - Physiological and behavioral plasticity allows animals to adapt to changes in
external (environmental) and internal (physiological) factors. In insects, the
physiological state modulates adult behavior in response to different odorant
stimuli. Hormones have the potential to play a major role in the plasticity of
the olfactory responses. To explore if peripheral olfactory processing could be
regulated by steroid hormones, we characterized the molecular,
electrophysiological, and behavioral response to changes in endogenous hormone
levels in adult male Spodoptera littoralis. The expression of the receptor
complex (EcR/USP) was localized by in situ hybridization in the olfactory
sensilla of antennae. Injections of 20-hydroxyecdysone (20E) induced an
ecdysteroid signaling pathway in antennae and increased expression of the nuclear
receptors EcR, USP and E75. Diacylglycerol kinase (DGK) and CaM expression were
also up-regulated by 20E. Taken together, these molecular, electrophysiological,
and behavioral results suggest a hormonal regulation of the peripheral olfactory
processing in S. littoralis.
PMID- 22044720
TI - KHA-CARI guideline: biochemical and haematological targets: haemoglobin
concentrations in patients using erythropoietin-stimulating agents.
PMID- 22044721
TI - Human leukocyte antigen-G 3' untranslated region polymorphisms are associated
with better kidney allograft acceptance.
AB - Human leukocyte antigen-G (HLA-G) plays a well-recognized role in the modulation
of the immune response, and HLA-G expression has been associated with increased
graft survival and decreased rejection episodes. To investigate the role of the
HLA-G 3' untranslated region (3'UTR) in renal transplantation, we evaluated
several polymorphic sites (14-bp Del/Ins +3003T/C, +3010C/G, +3027C/A, +3035C/T,
+3142G/C, and +3187A/G) in patients exhibiting or not exhibiting rejection
episodes. A total of 104 patients (15 with acute and 48 with chronic rejection,
and 41 with no rejection) and 142 healthy individuals were studied. HLA-G 3'UTR
was typed by direct sequencing. The +3035C-C genotype was more frequent in
patients exhibiting chronic rejection compared with healthy controls, and the
+3035C-T genotype was less frequent in chronic rejection compared with patients
without rejection (acute plus chronic) or compared with healthy controls. The
+3187G-A genotype, in which the A allele is associated with increased mRNA
degradation, showed increased frequency in the rejection group (acute plus
chronic) when compared with healthy controls. The 14 base pair Deletion/Insertion
genotype was marginally increased in patients with acute rejection. This is the
first study to show associations among numerous polymorphic sites in the HLA-G
3'UTR in kidney allotransplantation, which may contribute to the understanding of
HLA-G post-transcriptional mechanisms.
PMID- 22044722
TI - Epidural varicosis as a possible cause of radicular pain: a case report.
AB - INTRODUCTION: The incidence rate of epidural varicosis has declined by 0.07% to
1.2% since the introduction of computed tomography and magnetic resonance
imaging. Despite the use of these modern imaging methods it can still be
difficult to distinguish the diagnosis of epidural varicosis from other causes,
such as nucleus pulposus prolapse. CASE PRESENTATION: We present the case of a 48
year-old Caucasian woman who had been experiencing sciatic pain for seven years.
A physical examination showed nerve root pain at L5 on the right side, with
positive signs of neurotension. During an elective hysterectomy due to
endometriosis, unusually pronounced varicosis in her lesser pelvis was seen that
had not previously been detected. Postoperatively, our patient developed a
symptomatic pulmonary embolism. Findings from magnetic resonance tomography of
her lumbar spine, in conjunction with our patient's history, were considered by
the radiologist to be indicative of epidural varicosis. No further pathological
abnormalities that could have been the cause of the nerve root pain were found.
CONCLUSIONS: In cases of epidural varicosis with irritation of neural structures
as a result of inferior vena cava hypoplasia, surgical treatment leads to
unsatisfactory results. Significantly better results can be achieved by resolving
the cause of the vena cava pathology. In cases of hypoplasia or aplasia of the
inferior vena cava this is not always possible; consequently, as in the case of
our patient, only a symptomatic therapy in combination with an anticoagulant and
compression therapy can be performed.
PMID- 22044723
TI - Generation of the first BAC-based physical map of the common carp genome.
AB - BACKGROUND: Common carp (Cyprinus carpio), a member of Cyprinidae, is the third
most important aquaculture species in the world with an annual global production
of 3.4 million metric tons, accounting for nearly 14% of the all freshwater
aquaculture production in the world. Apparently genomic resources are needed for
this species in order to study its performance and production traits. In spite of
much progress, no physical maps have been available for common carp. The
objective of this project was to generate a BAC-based physical map using
fluorescent restriction fingerprinting. RESULT: The first generation of common
carp physical map was constructed using four- color High Information Content
Fingerprinting (HICF). A total of 72,158 BAC clones were analyzed that generated
67,493 valid fingerprints (5.5 * genome coverage). These BAC clones were
assembled into 3,696 contigs with the average length of 476 kb and a N50 length
of 688 kb, representing approximately 1.76 Gb of the common carp genome. The
largest contig contained 171 BAC clones with the physical length of 3.12 Mb.
There are 761 contigs longer than the N50, and these contigs should be the most
useful resource for future integrations with linkage map and whole genome
sequence assembly. The common carp physical map is available at
http://genomics.cafs.ac.cn/fpc/WebAGCoL/Carp/WebFPC/. CONCLUSION: The reported
common carp physical map is the first physical map of the common carp genome. It
should be a valuable genome resource facilitating whole genome sequence assembly
and characterization of position-based genes important for aquaculture traits.
PMID- 22044724
TI - Short women with severe sepsis-related acute lung injury receive lung protective
ventilation less frequently: an observational cohort study.
AB - INTRODUCTION: Lung protective ventilation (LPV) has been shown to improve
survival and the duration of mechanical ventilation in acute lung injury (ALI)
patients. Mortality of ALI may vary by gender, which could result from treatment
variability. Whether gender is associated with the use of LPV is not known.
METHODS: A total of 421 severe sepsis-related ALI subjects in the Consortium to
Evaluate Lung Edema Genetics from seven teaching hospitals between 2002 and 2008
were included in our study. We evaluated patients' tidal volume, plateau pressure
and arterial pH to determine whether patients received LPV during the first two
days after developing ALI. The odds ratio of receiving LPV was estimated by a
logistic regression model with robust and cluster options. RESULTS: Women had
similar characteristics as men with the exception of lower height and higher
illness severity, as measured by Acute Physiology and Chronic Health Evaluation
(APACHE) II score. 225 (53%) of the subjects received LPV during the first two
days after ALI onset; women received LPV less frequently than men (46% versus
59%, P < 0.001). However, after adjustment for height and severity of illness
(APACHE II), there was no difference in exposure to LPV between men and women (P
= 0.262). CONCLUSIONS: Short people are less likely to receive LPV, which seems
to explain the tendency of clinicians to adhere to LPV less strictly in women.
Strategies to standardize application of LPV, independent of differences in
height and severity of illness, are necessary.
PMID- 22044725
TI - Unusual systemic metastases of malignant seminoma in a dog.
AB - Unilateral enlargement of left testicle and scrotum was detected in an 8-year-old
West Highland White Terrier. The histopathological diagnosis after surgery was a
seminoma (SEM) tumour, and a diagnosis of metastatic foci was also detected in
vaginal tunic and scrotum. Two months later, new metastatic SEM foci in the skin
were diagnosed. Twenty-two months after the initial orchiectomy new multiple
cutaneous nodules and a swelling of periesophageal structures were observed.
Finally, the necropsy revealed multiple malignant metastatic SEM focus. To the
author's knowledge, this is the first description of a canine SEM with unusual
widespread metastasis on the base of tongue, soft palate, trachea and
pericardium.
PMID- 22044726
TI - A novel method to detect accidental oesophageal intubation based on ventilation
pressure waveforms.
AB - BACKGROUND: Emergency endotracheal intubation results in accidental oesophageal
intubation in up to 17% of patients. This is frequently undetected thereby adding
to the morbidity and mortality. No current method to detect accidental
oesophageal intubation in an emergency setting is both highly sensitive and
specific. We hypothesized that, based on differences between the mechanical
properties of the oesophagus and the trachea/lung, ventilation pressures could
discriminate between tracheal and oesophageal intubation. Such a technique would
potentially not suffer some of the limitations of current methods to detect
oesophageal intubation in emergency conditions such as noisy environment (making
clinical assessment difficult) or low/no flow states (reducing the applicability
of capnometry). The aim of our study was thus to develop and assess a technique
that may more rapidly and accurately differentiate oesophageal from tracheal
intubation based on airway pressure gradients. MATERIALS AND METHODS: Forty adult
patients undergoing elective surgery were included. In 20 patients the trachea
was intubated with an endotracheal tube; in 20 patients the oesophagus was
purposefully intubated using an Easytube((r)) (Rush, Germany). In all patients, a
thin air-filled catheter was inserted through the tube lumen until its tip was
1cm from the distal end, and connected to a pressure transducer. Pressure was
recorded simultaneously from a second catheter at the proximal end of the tube.
For the first three manual ventilations in each patient, a parameter (D) based on
temporal (dP/dt) and spatial (dP/ds) pressure gradients (and reflecting flow
divided by elastance) was calculated and evaluated for its ability to
discriminate between oesophageal and tracheal intubation. RESULTS AND DISCUSSION:
For all tracheal ventilations, D-values were >0.5 (range 0.6-47.9), while for all
oesophageal ventilations D-values were <0.5 (range 0.0005-0.07). CONCLUSION: This
technique has the potential to provide a diagnosis of failed intubation within
seconds with high sensitivity and specificity.
PMID- 22044727
TI - Differential diagnosis and therapy of leg ulcers.
AB - A leg ulcer is a symptom and the treating physician needs to find out its origin
by differential diagnostic approaches and procedures. The correct diagnosis leads
to a specific therapy that ideally accelerates the healing of the ulceration.
Identifying the pathogenesis of a leg ulcer is the first and main step towards
healing. Although vascular diseases are the major causes of leg ulcers, one needs
to consider, in addition to venous and arterial disorders, autoimmune,
infectious, metabolic and neoplastic causes. The simple truth that one can only
make a diagnosis that was considered holds particularly true in leg ulcers. The
differential diagnostic considerations presented here appear in the daily routine
of a dermatologist and the article provides help in diagnostic approaches and
therapeutic decisions.
PMID- 22044728
TI - The role of ultrasonography in the diagnosis of the musculo-skeletal problems of
haemophilia.
AB - Recurrent haemarthrosis is the final cause of haemophilic arthrosic disease in
haemophilia patients. Therefore, it is essential to diagnose it early, both
clinically and by imaging. In addition, haemophilia patients experience chronic
synovitis, joint degeneration, muscle haematoma and pseudotumours. The objective
of this article is to highlight the value of ultrasounds in the diagnosis and
control of the evolution of musculo-skeletal problems in haemophilia patients. To
this end, we have performed a literature search in the PubMed, Web of
Science((r)) (WOS) and SciVerse bases, using the following keywords: hemophilia
or haemophilia and ultrasonography (US), ultrasound, echography and sonography.
The search was limited to studies published in English between the years 1991 and
2011, finding a total of 221 references. After reviewing the title or abstract
for evidence of the use of US for the diagnosis of musculo-skeletal lesions in
haemophilia, we selected 24 of these references. We added data collected from our
experience to the most important data found in the references. Our main
conclusion is that US is highly valuable for the diagnosis of musculo-skeletal
diseases in haemophilia. It is a fast, effective, safe, available, comparative,
real-time technique that can help us confirm the clinical examination. It is
particularly important in acute haemarthrosis, as it can be used to objectively
identify the presence of blood in the joints, measure its size, pinpoint its
location, assess its evolution and confirm its complete disappearance.
PMID- 22044729
TI - Left ventricular function and exercise capacity in patients with slow coronary
flow.
AB - BACKGROUND: Endothelial and microvascular dysfunction have been implicated in
slow coronary flow (SCF). How and to what extent do these etiological factors
affect left ventricular (LV) function and exercise capacity? AIM: The aim of the
study was to evaluate LV systolic and diastolic function by pulsed tissue Doppler
imaging (TDI) in SCF patients and their effects on exercise capacity. SUBJECTS
AND METHODS: Sixty SCF patients and 20 control subjects were included in the
study. Echocardiographic examination, treadmill exercise test, and TDI were
performed. Isovolumic myocardial acceleration (IVA) and myocardial performance
index (MPI) were measured. RESULTS: TDI mean parameters for systolic and
diastolic LV function were significantly impaired in SCF group with decreased Sa,
IVA, Ea/Aa, and increased MPI (0.31 +/- 0.06 vs. 0.26 +/- 0.04, P < 0.01)
compared to control. There was significant correlation between thrombolysis in
myocardial infarction (TIMI) frame count and TDI mean parameters for LV systolic
function (Sa & IVA, r =-0.53, P < 0.01 & r =-0.36, P < 0.05, respectively). Mean
TIMI frame count was correlated with MPI and E/Ea. SCF patients had poorer peak
exercise capacity than the controls (9.9 +/- 1.9 METs vs. 12.7 +/- 2.3, P < 0.01)
with significant negative correlation with mean TIMI frame count (r =-0.46, P <
0.01). CONCLUSION: There is impairment of LV systolic and diastolic function in
SCF patients with clinical impact on exercise capacity which emphasizes the
importance of close follow-up of these patients for risk stratification.
PMID- 22044730
TI - Novel scoring system as a useful model to predict the outcome of patients with
acute liver failure: Application to indication criteria for liver
transplantation.
AB - AIM: In Japan, the indication for liver transplantation in patients with acute
liver failure (ALF) is currently determined according to the guideline published
in 1996. However, its predictive accuracy has fallen in recent patients. Thus, we
attempted to establish a new guideline. METHODS: The subjects were 1096 ALF
patients enrolled in a nationwide survey. All patients showed a prothrombin time
<40% of the standardized value and grade II or more severe hepatic
encephalopathy. A multiple logistic regression analysis and receiver operating
characteristic analysis were performed in 698 patients seen between 1998 and 2003
to identify significant parameters determining the outcome of patients. The
extracted parameters were graded as numerical scores. An established scoring
system was validated in patients seen between 2004 and 2008. RESULTS: Six
parameters were identified and graded as 0, 1 and/or 2; the interval between
disease onset and development of hepatic encephalopathy, prothrombin time, serum
total bilirubin concentration, the ratio of direct to total bilirubin
concentration, peripheral platelet count and the presence of liver atrophy. When
the prognosis of the patients with total score of 5 or more was judged as
"death", the predictive accuracy was 0.80 with sensitivity, specificity, positive
predictive value and negative predictive value greater than 0.70. The values were
similarly high in patients for validation. CONCLUSION: Novel scoring system for
predicting the outcome of ALF patients may be useful to determine the indication
of liver transplantation, since the system showed high predictive accuracy even
after validation.
PMID- 22044731
TI - I-Stent for treatment of angle recession with raised intraocular pressure.
PMID- 22044732
TI - Effect of high hydrostatic pressure processing on norovirus infectivity and
genome stability in strawberry puree and mineral water.
AB - We report an evaluation of the effect of various combinations of pressures and
times on the inactivation of norovirus (NoV) in two types of matrices that are
important in NoV transmission: water and soft fruits. The human NoV surrogate
murine norovirus was used as the model virus. The effect of HHP on the viral
genome was evaluated by using RT real-time PCR (RT-qPCR), and infectivity assay
was used to assess effects on the ability of the virus to attach to and replicate
in cells. HHP treatments of 400 MPa for 2.5 min proved to be sufficient for
efficient inactivation of NoV (>99.9% reduction). The efficacy of viral
inactivation was highly dependent on the matrix in which the virus was present.
Therefore, the effect of HHP should be carefully studied in all matrices to which
HHP could potentially be applied. Finally, we found no consistent correlation
between RT-qPCR and virus infectivity results, and consequently RT-qPCR is not a
satisfactory tool for predicting risks to human health.
PMID- 22044733
TI - Bond strength and interfacial micromorphology of etch-and-rinse and self-adhesive
resin cements to dentin.
AB - PURPOSE: To evaluate the microtensile bond strength and interfacial
micromorphology of indirect composite restorations to dentin using three
commercial resin cements after 24 hours and 30 days of water storage. MATERIALS
AND METHODS: The medium dentin of third human molars was exposed (N = 30, n = 10
per group). Three commercial resin cements were used to cement indirect resin
composite restorations to dentin: the auto-cured C&B Cement/All Bond 2, the dual
cured RelyX ARC/Adper Single Bond 2, and the self-adhesive dual-cured RelyX
Unicem. Teeth were sectioned after water storage at 37 degrees C (24 hours and 30
days) to obtain beams with a bonded area of 0.8 mm(2) . The specimens were tested
in a universal testing machine at a 0.5 mm/min crosshead speed. Scanning electron
microscopic fractographic and interfacial micromorphology analyses were
performed. Data were analyzed using two-way ANOVA and Tukey's test (alpha= 0.05).
RESULTS: Mean bond strength (MPa) after 24 hours: C&B Cement 19.5 +/- 3.8, RelyX
ARC 40.8 +/- 9.4, RelyX Unicem 31.3 +/- 7.4; after 30 days: C&B Cement 24.5 +/-
5.1, RelyX ARC 44.2 +/- 8.5, RelyX Unicem 28.3 +/- 7.1. The mean bond strengths
of both dual-cure cements were significantly higher than that obtained with C&B
Cement after 24 hours. A significant increase in the bond strength of C&B Cement
was verified after 30 days, reaching values statistically equivalent to those
produced by RelyX Unicem and RelyX ARC. The self-adhesive cement preserved the
same level of bond strength after 30 days. Fractographic analysis revealed a
prevalence of cohesive fractures in the hybrid layer for C&B Cement, mixed
(cohesive in the cement, hybrid layer, and adhesive) for RelyX ARC, and cohesive
in the cement for RelyX Unicem. No distinguishable hybrid layer or resin tags
were observed in the interaction of RelyX Unicem with dentin. CONCLUSIONS: The
particular interaction of each cement with dentin results in specific bond
strength and failure patterns that varied among groups in both evaluation times.
Even though the self-adhesive cement tested exhibited no authentic hybrid layer,
it was able to promote reliable adhesion with the underlying dentin.
PMID- 22044734
TI - Cognitive symptoms are common in immune thrombocytopenia and associate with
autonomic symptom burden.
AB - OBJECTIVES: People with adult immune thrombocytopenia (ITP) are commonly thought
to have an isolated blood disorder, but many also describe memory and
concentration problems. Cognitive impairment commonly associates with autonomic
dysfunction. Here, we quantified cognitive symptoms in a large cohort of patients
with ITP compared with controls and explored the relationship with autonomic
symptoms. METHODS: Patients with ITP were approached in the UK via the national
ITP Support Association and invited to complete Composite Autonomic Symptom Scale
(COMPASS; measure of autonomic symptoms) and Cognitive Failures Questionnaire
(CFQ) together with one from a friend of similar age and sex without ITP.
RESULTS: Three hundred and ninety-eight patients with ITP completed measures with
paired data from a representative group of 189 patients and controls (47%). Both
autonomic and cognitive symptom burden were higher in ITP compared with controls
(COMPASS score (48 +/- 14 vs. 38 +/- 12; P > 0.0001); CFQ (43 +/- 17 vs. 36 +/-
13; P < 0.0001). A positive relationship was seen between increasing cognitive
symptoms and higher COMPASS score (P < 0.0001; r(2) = 0.1). Increasing cognitive
symptoms did not associate with platelet count (P = 0.08, r(2) = 0.008).
Multivariate analysis confirmed age and COMPASS independently associated with
higher CFQ but not platelet count. CONCLUSION: Immune thrombocytopenia is more
than a bleeding disorder; cognitive symptoms are common and independently
associate with autonomic symptoms but not disease severity.
PMID- 22044735
TI - Silencing of ICERs (Inducible cAMP Early Repressors) results in partial
protection of neurons from programmed cell death.
AB - ICERs proteins (Inducible cAMP Early Repressors) are the most effective
endogenous repressors of CREB/CREM/ATF transcription factors family (CREB-cAMP
Responsive Element Binding protein, CREM-cAMP Responsive Element Modulator, ATF
Activating Transcription Factor) that have repeatedly been shown to have a
prosurvival function. It has been reported previously that neuronal death is
accompanied by increased expression of ICERs and, furthermore, their
overexpression provokes neuronal cell death in culture. However, it was not
explained whether endogenously activated by proapoptotic stimuli ICERs contribute
to the neuronal cell death. Herein, we have examined the involvement of
endogenous ICERs in the apoptosis by checking whether it is possible to protect
neurons from cell death by blocking the ICER gene. We applied two different in
vitro models of neuronal death of primary neuronal cultures: excitotoxic death of
neurons derived from dentate gyrus, and cortical cell loss provoked by trophic
deprivation. Using the lentiviral vector (LV) to deliver shRNA, specifically
silencing ICERs, but not other CREM proteins, we have found that silencing of
ICERs enhances the CRE-driven transcription and exerts a mild, although
significant, neuroprotective effect in both models. Since we demonstrated that
silencing of endogenous ICERs have protective effect on neurons exposed to
apoptosis-provoking conditions, targeting ICERs might be a novel strategy to
prevent neuronal loss during degenerative processes.
PMID- 22044736
TI - A prolonged experimental febrile seizure results in motor map reorganization in
adulthood.
AB - INTRODUCTION: Clinical studies have suggested that children experiencing a
febrile seizure (FS) before the age of 1year have persistent deficits, but it is
unknown whether these seizures lead to permanent cortical reorganization and
alterations in function. A FS on the background of increased genetic seizure
susceptibility may also lead to negative long-term consequences. Alterations in
neocortical motor map expression provide a measure of neocortical reorganization
and have been reported in both adults with frontal lobe epilepsy and following
seizure induction in experimental models. The objectives of the present study
were to determine whether (1) an infantile FS leads to changes to motor map
expression in adulthood; (2) long-term cortical reorganization is a function of
the age at FS or genetic seizure susceptibility; and (3) different levels of
GABA(A) or glutamate receptor subunits or cation-chloride-co-transporters (CCCs)
at the time of FS correlate with alterations to motor map expression. MATERIALS
AND METHODS: FSs were induced in postnatal day 10 (P10) or P14 Long-Evans (LE)
rats or in P14 seizure-prone FAST rats by the administration of the bacterial
endotoxin lipopolysaccharide (LPS) and a subconvulsant dose of kainic acid. Ten
weeks later intracortical microstimulation was performed to generate motor maps
of forelimb movement representations. Sensorimotor neocortex samples were also
dissected from naive P10 FAST and P10 and P14 LE pups for western blotting with
antibodies against various GABA(A), NMDA, and AMPA receptor subunits and for
CCCs. RESULTS: Adult FAST rats had larger motor maps with lower stimulation
thresholds after a FS at P14, while adult LE rats had significantly lower map
stimulation thresholds but similar sized maps after a FS at P10 compared to
controls. There were no differences in neocortical motor map size or stimulation
thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had
significantly lower levels of the GABA(A) receptor alpha1 subunit, higher levels
of the alpha2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex
compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of
the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the
P14 LE rats. CONCLUSIONS: A single infantile FS can have long-term effects on
neocortical reorganization in younger individuals and those with underlying
seizure susceptibility. These changes may be related to an increased level of
excitability in the neocortex of younger or genetically seizure-prone rats, as
suggested by immaturity of their GABAergic and CCC systems. Given the high
incidence of FSs in children, it will be important to gain a better understanding
of how age and genetic seizure predisposition may contribute to the long-term
sequelae of these events.
PMID- 22044737
TI - Transcriptional changes in adhesion-related genes are site-specific during noise
induced cochlear pathogenesis.
AB - Cell-cell junctions and junctions between cells and extracellular matrix are
essential for maintenance of the structural and functional integrity of the
cochlea, and are also a major target of acoustic trauma. While morphological
assessments have revealed adhesion dysfunction in noise-traumatized cochleae, the
molecular mechanisms responsible for adhesion disruption are not clear. Here, we
screened the transcriptional expression of 49 adhesion-related genes in normal
rat cochleae and measured the expression changes in the early phases of cochlear
pathogenesis after acoustic trauma. We found that genes from four adhesion
families, including the immunoglobulin superfamily and the integrin, cadherin,
and selectin families, are expressed in the normal cochlea. Exposure to an
intense noise at 120dB sound pressure level (SPL) for 2h caused site-specific
changes in expression levels in the apical and the basal sections of the sensory
epithelium. Expression changes that occurred in the cochlear sensory epithelium
were biphasic, with early upregulation at 2h post-noise exposure and subsequent
downregulation at 1day post-exposure. Importantly, the altered expression level
of seven genes (Sgce, Sell, Itga5, Itgal, Selp, Cntn1 and Col5a1) is related to
the level of threshold shift of the auditory brainstem response (ABR), an index
reflecting functional change in the cochlea. Notably, the genes showing
expression changes exhibited diverse constitutive expression levels and belong to
multiple adhesion gene families. The finding of expression changes in multiple
families of adhesion genes in a temporal fashion (2h vs. 1day) and a spatial
fashion (the apical and the basal sensory epithelia as well as the lateral wall
tissue) suggests that acoustic overstimulation provokes a complex response in
adhesion genes, which likely involves multiple adhesion-related signaling
pathways.
PMID- 22044739
TI - Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of
revaccination of non-responders and duration of protection.
AB - BACKGROUND: Hepatitis B vaccination is recommended for patients on hemodialysis,
however, seroprotection after a primary vaccine series is suboptimum. Limited
data are available on the effect of revaccination of non-responders and on
persistence of immunity in this population. METHODS: Hepatitis B vaccine (40
MUg/dose) was given to 77 susceptible patients on hemodialysis (0, 1, and 6 month
schedule). Levels of hepatitis B surface antibody (anti-HBs) were tested >= 28
days after the third dose was administered, and non-responders revaccinated with
an additional 3-dose series. Vaccine responders (anti-HBs >=10 mIU/mL) were re
tested every 6 months and booster doses given as needed. Kaplan-Meier survival
curve was used to estimate the probability of maintaining protective antibody
level. Cox-proportional hazards models were used to assess the association
between time to loss of protective antibody levels and certain explanatory
variables. RESULTS: Overall primary vaccine-induced response was 79.2% (95% CI
68.2%, 87.3%), including 49/77 (63.6%; 95% CI 51.8%, 74.7%) patients who received
the initial primary hepatitis B vaccine series and 12/21 (57.1%; 95% CI 34.4%,
77.4%) non-responders who were revaccinated with an additional series. Among weak
responders (anti-HBs level 10.0-99.9 mIU/mL), protective antibody levels
persisted in 44% for 12 months post-vaccination; whereas among strong responders
(anti-HBs level >=100 mIU/mL), protective antibody levels persisted in 92% for 12
months, and 68% for 24 months post-vaccination. A weak post-vaccination response
increased the risk of losing protective antibody levels (adjusted hazard ratio,
9.7; 95% confidence interval, 3.5-28.5; p<0.0001). CONCLUSION: Revaccinating
patients undergoing hemodialysis who do not respond to a primary vaccine series
substantially increases the pool of protected patients. The threshold for
defining hepatitis B vaccine-induced immunity should be revisited in this patient
population to maximize the duration of protection.
PMID- 22044738
TI - Evaluation of SLOG/TCI-III pediatric system on target control infusion of
propofol.
AB - BACKGROUND: The target-controlled infusion-III (SLOG/TCI-III) system was derived
from a model set up by the local pediatric population for target control infusion
of propofol. METHODS: The current study aimed at evaluating the difference
between target concentrations of propofol and performance, which was measured
using the SLOG/TCI-III system in children. Thirty children fulfilling the I-II
criteria according to American Society of Anesthesiology were enrolled in the
study. The target plasma concentration of propofol was fed into the SLOG/TCI-III
system and compared with the measured concentrations of propofol. Blood samples
were collected and analyzed by high performance liquid chromatography with
fluorescence detector. The performance error (PE) was determined for each
measured blood propofol concentration. The performances of the TCI-III system
were determined by the median performance error (MDPE), the median absolute
performance error (MDAPE), and Wobble (the median absolute deviation of each PE
from the MDPE), respectively. RESULTS: Concentration against target concentration
showed good linear correlation: concentration = 1.3428 target concentration -
0.2633 (r = 0.8667). The MDPE and MDAPE of the pediatric system were 10 and 22%,
respectively, and the median value for Wobble was 24%. MDPE and MDAPE were less
than 15 and 30%, respectively. CONCLUSIONS: The performance of TCI-III system
seems to be in the accepted limits for clinical practice in children.
PMID- 22044740
TI - Knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations
in a low-income, public health clinic population.
AB - OBJECTIVE: The Public Health Center Vaccine Survey (PHCVS) examines the
knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations
in a largely low-income, urban, public health clinic population in Los Angeles
County, USA. DESIGN: A cross-sectional survey of vulnerable individuals at risk
for severe influenza infection was conducted in one of the nation's largest local
public health jurisdictions. SUBJECTS: A total of 1541 clinic patients were
recruited in the waiting rooms of five large public health centers in Los Angeles
County from June to August, 2010. RESULTS: Among prospective respondents who met
eligibility criteria, 92% completed the survey. The majority was black or Latino
and most were between the ages of 18 and 44 years. More than half were
unemployed; two-thirds had no health insurance; and nearly one-half reported
having a high school education or less. About one-fifth reported they had
received the H1N1 vaccine during the previous flu season. In comparative
analyses, negative beliefs about vaccine safety and efficacy were highly
predictive of H1N1 vaccination. Blacks were less likely than non-black
respondents to report receiving the H1N1 vaccine (OR=0.7, 95% CI=0.6-1.0). Blacks
were also less likely than other respondents to agree that vaccines can prevent
disease (OR=0.4, 95% CI=0.3-0.5), that vaccines are safe (OR=0.5, 95% CI=0.4
0.6), and that they trust doctors/clinicians who recommend vaccines (OR=0.5, 95%
CI=0.4-0.7). CONCLUSIONS: Study findings provide a useful risk profile of
vulnerable groups in Los Angeles County, which may be generalizable to other
urban jurisdictions in the United States. They also describe real world
situations that can be used to forecast potential challenges that vaccine beliefs
may pose to national as well as local influenza pandemic planning and response,
especially for communities with limited access to these preventive services.
PMID- 22044741
TI - Immunological adjuvant efficacy of glycyrrhetinic acid liposome against Newcastle
disease vaccine.
AB - The aim of this study is to investigate whether the activity of inducing immune
response of glycyrrhetinic acid (GA) could be enhanced after GA was encapsulated
with liposome. Three hundred and fifty 14-day-old chickens were randomly assigned
to 7 groups and vaccinated with Newcastle disease (ND) vaccine. Simultaneously,
the chickens in experimental groups were injected with the glycyrrhetinic acid
liposome (GAL) at three doses, GA and blank liposome, respectively. The activity
of serum antibody titer, concentrations of immunoglobulins G (IgG) and
immunoglobulins M (IgM), lymphocytes proliferation, the proportions of lymphocyte
subpopulations (CD4(+) and CD8(+)) was determined after vaccination. GAL was
evaluated for inducing humoral immunity and cellular immunity in chicken against
Newcastle disease (ND) vaccine. The results showed that GAL not only could
significantly enhance the antibody titers, IgG and IgM in ND vaccine immunized
chicken, but also significantly promote the lymphocyte proliferation and the
proportions of CD4(+) and CD8(+), as comparison with GA, BL and VC control
groups. Moreover, the effects appear a dose-dependent manner and a time-dependent
manner. These indicated that GAL could significantly promote the activation
potential of humoral immunity and cellular immunity in chicken and present
certain dose-effect and time-effect relationships. The formulations of GA and
liposome can further enhance the immune response against ND vaccine compared with
the adjuvant alone.
PMID- 22044742
TI - Control of methicillin resistant Staphylococcus aureus infection utilizing a
novel immunostimulatory peptide.
AB - The emergence of community-acquired methicillin-resistant Staphylococcus aureus
(CA-MRSA) is a serious health concern worldwide that requires new therapeutic
approaches that extend beyond the development and use of new antibiotics. In this
study, a conformationally biased, response-selective agonist of human C5a, known
as EP67, was used to induce host innate immunity as a therapeutic method of
reducing CA-MRSA infections. Using a murine model of dermonecrosis we show that
EP67 treatment effectively limits CA-MRSA infection by promoting cytokine
synthesis and neutrophil influx. In contrast, EP67 was ineffective in reducing
lesion formation in C5a receptor (CD88(-/-)) knockout mice, indicating that EP67
activates host innate immunity by engagement of CD88 bearing cells. These results
suggest that EP67 may serve as a novel immunotherapeutic for prevention and
treatment of CA-MRSA dermal infection.
PMID- 22044743
TI - Comparative analysis of the complete genome sequences of two Australian origin
live attenuated vaccines of infectious laryngotracheitis virus.
AB - Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes
acute respiratory disease in poultry. Live attenuated ILTV vaccines have been
used extensively to help control outbreaks of disease. Two Australian-origin
attenuated vaccine strains, SA2 and A20 ILTV, are commercially available and are
in frequent use in Australia. Both these vaccines are of chicken embryo origin
(CEO). The A20 ILTV strain was developed from the SA2 ILTV strain by sequential
passage of SA2 ILTV in tissue culture in order to reduce its residual virulence.
Previous studies in our laboratories have demonstrated the greater attenuation of
A20 ILTV under controlled experimental conditions, but the genetic basis of the
in vivo phenotypes of A20 and SA2 ILTV has not been elucidated. In this study,
the genetic differences between A20 and SA2 ILTV were examined by performing
complete genome sequencing and comparative analysis. The genome sequences were
also compared to a reference sequence from another CEO ILTV vaccine (Serva ILTV:
GenBank accession number HQ_630064) of European-origin. Additional in ovo studies
to assess cell to cell spread were performed in order to allow further
comparisons of the pathogenicity of SA2 and A20 ILTV. The sequencing results
showed that the genome sizes of SA2 and A20 ILTV were 152,975 and 152,978bp,
respectively, while Serva ILTV had a genome size of 152,630bp. The genomes of SA2
and A20 ILTV shared 99.9% nucleotide sequence identity with each other, but only
99.2% identity with Serva ILTV. In complete genome alignments between SA2 and A20
ILTV, a total of 24 single nucleotide polymorphisms (SNPs) were identified, but
only two of these were non-synonymous. These were located in the ORF B and UL15
genes. Four indels were detected in non-coding regions. The findings from this
study demonstrate the general genetic stability of ILTV, but also show that non
synonymous changes in the ORF B and UL15 genes have arisen following tissue
culture passage of SA2 ILTV to produce the A20 vaccine. It is likely that these
non-synonymous changes are related to the greater attenuation of A20 ILTV
compared to SA2 ILTV, and to the reduced ability of A20 ILTV to spread from cell
to cell, as observed in this study. The results from this study also demonstrate
the divergence between the genomes of the Australian-origin ILTV vaccine strains
and the Serva vaccine strain.
PMID- 22044744
TI - Improving inpatient postnatal services: midwives views and perspectives of
engagement in a quality improvement initiative.
AB - BACKGROUND: Despite major policy initiatives in the United Kingdom to enhance
women's experiences of maternity care, improving in-patient postnatal care
remains a low priority, although it is an aspect of care consistently rated as
poor by women. As part of a systems and process approach to improving care at one
maternity unit in the South of England, the views and perspectives of midwives
responsible for implementing change were sought. METHODS: A Continuous Quality
Improvement (CQI) approach was adopted to support a systems and process change to
in-patient care and care on transfer home in a large district general hospital
with around 6000 births a year. The CQI approach included an initial assessment
to identify where revisions to routine systems and processes were required,
developing, implementing and evaluating revisions to the content and
documentation of care in hospital and on transfer home, and training workshops
for midwives and other maternity staff responsible for implementing changes. To
assess midwifery views of the quality improvement process and their engagement
with this, questionnaires were sent to those who had participated at the outset.
RESULTS: Questionnaires were received from 68 (46%) of the estimated 149 midwives
eligible to complete the questionnaire. All midwives were aware of the revisions
introduced, and two-thirds felt these were more appropriate to meet the women's
physical and emotional health, information and support needs. Some midwives
considered that the introduction of new maternal postnatal records increased
their workload, mainly as a consequence of colleagues not completing
documentation as required. CONCLUSIONS: This was the first UK study to undertake
a review of in-patient postnatal services. Involvement of midwives at the outset
was essential to the success of the initiative. Midwives play a lead role in the
planning and organisation of in-patient postnatal care and it was important to
obtain their feedback on whether revisions were pragmatic and achieved
anticipated improvements in care quality. Their initial involvement ensured
priority areas for change were identified and implemented. Their subsequent
feedback highlighted further important areas to address as part of CQI to ensure
best quality care continues to be implemented. Our findings could support other
maternity service organisations to optimise in-patient postnatal services.
PMID- 22044745
TI - Red blood cell transfusion and increased length of storage are not associated
with deep vein thrombosis in medical and surgical critically ill patients: a
prospective observational cohort study.
AB - INTRODUCTION: With prolonged storage times, cell membranes of red blood cells
(RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'.
Storage lesions may promote inflammation and thrombophilia when transfused. In
trauma patients, RBC transfusion was an independent risk factor for deep vein
thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or
more units were transfused. The objective of this study was to determine if RBC
transfusions or RBC storage age predicts incident DVT in medical or surgical
intensive care unit (ICU) patients. METHODS: Using a database which prospectively
enrolled 261 patients over the course of 1 year with an ICU stay of at least 3
days, we analyzed DVT and RBC transfusions using Cox proportional hazards
regression. Transfusions were analyzed with 4 thresholds, and storage age using 3
thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds.
Multivariable analyses were adjusted for 4 significant DVT predictors in this
population (venous thrombosis history, chronic dialysis, platelet transfusion and
inotropes). RESULTS: Of 261 patients, 126 (48.3%) had at least 1 RBC transfusion;
46.8% of those transfused had >= 5 units in ICU. Patients receiving RBCs were
older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker
(APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05).
The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was
4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC
exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage
(<= 7 or > 7 days, <= 14 or > 14 days, <= 21 or > 21 days). Among patients
transfused, no multivariable analyses showed that RBC transfusion or storage age
predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for <= 7
days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1).
CONCLUSIONS: We were unable to detect any association between RBC transfusions or
prolonged red cell storage and increased risk of DVT in medical or surgical ICU
patients. Alternate explanations include a lack of sufficient events or patients'
interaction, between patient groups, a mixing of red cell storage times creating
differential effects on DVT risk, and unmeasured confounders.
PMID- 22044747
TI - Characteristics of the aberrant pyramidal tract in comparison with the pyramidal
tract in the human brain.
AB - BACKGROUND: The aberrant pyramidal tract (APT) refers to the collateral pathway
of the pyramidal tract (PT) through the medial lemniscus in the midbrain and
pons. Using diffusion tensor tractography (DTT), we investigated the
characteristics of the APT in comparison with the PT in the normal human brain.
RESULTS: In thirty-four (18.3%, right hemisphere: 20, left hemisphere: 14) of the
186 hemispheres, the APTs separated from the PT at the upper midbrain level,
descended through the medial lemniscus from the midbrain to the pons, and then
rejoined with the PT at the upper medulla. Nine (26.5%) of the 34 APTs were found
to originate from the primary somatosensory cortex without a primary motor cortex
origin. Values of fractional anisotropy (FA) and tract volume of the APT were
lower than those of the PT (P < 0.05); however, no difference in mean diffusivity
(MD) value was observed (P > 0.05). CONCLUSION: We found that the APT has
different characteristics, including less directionality, fewer neural fibers,
and less origin from the primary motor cortex than the PT.
PMID- 22044748
TI - Glycolic acid-g-chitosan-gold nanoflower nanocomposite scaffolds for drug
delivery and tissue engineering.
AB - This paper reports a simple novel method for the synthesis of flower like gold
nanoparticle (three dimensional branched nanoparticle) with >30 tips, under
controlled temperature condition. Formation of flower like Au nanoparticle was
confirmed by scanning electron microscopy (SEM) and transmission electron
microscopy (TEM). Next step of this paper reveals the potential use of novel
hybrids of chitosan-g-glycolic acid and gold nanoflower (AuNF) in controlled drug
delivery and tissue engineering applications. The drug loaded novel nanohybrid
scaffold is prepared by freeze drying of grafted polymer solution. Grafting of
glycolic acid to the chitosan and incorporation of drug were evaluated by Fourier
transform infrared spectroscopy (FTIR). The nanohybrid scaffolds were found to be
stable towards the pH of the medium. The cell viability study shows that prepared
nanohybrid scaffolds are biocompatible. Gold nanoflowers were found to control
the drug release rate in the buffer solution (pH 7.4). Therefore, for the
glycolic acid grafted chitosan based system, gold nanoflowers are the viable
additive for drug delivery.
PMID- 22044749
TI - Effects of the polysaccharide from Pholiota nameko on human cytokine network in
serum.
AB - Some physico-chemical characterizations of Pholiota nameko polysaccharides (PNPS
1) were studied, including sulfate content, UV/visible and infrared spectra, also
the variation of cytokine communication network in serum to clarify the
pharmacological effects of PNPS-1 by determination of 39 cytokines in serum of
healthy volunteers. The result proved that PNPS-1 possessed significant anti
inflammatory activity. Further, we use Microsoft Visio 2007 software to map out
the cell-cell communication network diagram. The analysis to the diagram
suggested that PNPS-1 could take effect on the innate and adaptive immunity and
hematopoiesis of volunteers.
PMID- 22044750
TI - Noncollagenous 16A domain of type XVII collagen-reactive CD4+ T cells play a
pivotal role in the development of active disease in experimental bullous
pemphigoid model.
AB - Bullous pemphigoid (BP), the most common autoimmune blistering disease, is caused
by autoantibodies against type XVII collagen (COL17). We recently demonstrated
that CD4+ T cells were crucial for the production of anti-COL17 IgG and for the
development of the BP phenotype by using a novel active BP mouse model by
adoptively transferring immunized splenocytes into immunodeficient COL17
humanized mice. Noncollagenous 16A (NC16A) domain of COL17 is considered to
contain the main pathogenic epitopes of BP, however, the pathogenicity of COL17
NC16A-reactive CD4+ T cells has never been elucidated. To address this issue, we
modulated the immune responses against COL17 in active BP model by using anti
CD40 ligand (CD40L) monoclonal antibody MR1, an inhibitor of the CD40-CD40L
interaction, in various ways. First, we show the essential role of CD4+ T cells
in the model by showing that CD4+ T cells isolated from wild-type mice immunized
with human COL17 enabled naive B cells to produce anti-COL17 NC16A IgG in vivo.
Second, we show that the activation of anti-COL17 NC16A IgG-producing B cells via
CD40-CD40L interaction was completed within 5 days after the adoptive transfer of
immunized splenocytes. Notably, a single administration of MR1 at day 0 was
enough to inhibit the production of anti-COL17 NC16A IgG and to diminish skin
lesions despite the presence of restored anti-COL17 IgG at the later stage. In
contrast, the delayed administration of MR1 failed to inhibit the production of
anti-COL17 NC16A IgG and the development of the BP phenotype. These results
strongly suggest that COL17 NC16A-reactive CD4+ T cells play a pivotal role in
the production of pathogenic autoantibodies and in the development of active
disease in experimental BP model.
PMID- 22044751
TI - Heritability and genome-wide association analysis of renal sinus fat accumulation
in the Framingham Heart Study.
AB - BACKGROUND: Ectopic fat accumulation in the renal sinus is associated with
chronic kidney disease and hypertension. The genetic contributions to renal sinus
fat accumulation in humans have not been well characterized. METHODS: The present
analysis consists of participants from the Framingham Offspring and Third
Generation who underwent computed tomography; renal sinus fat and visceral
adipose tissue (VAT) were quantified. Renal sinus fat was natural log transformed
and sex- and cohort-specific residuals were created, adjusted for (1) age, (2)
age and body mass index (BMI), and (3) age and VAT. Residuals were pooled and
used to calculate heritability using variance-components analysis in SOLAR. A
genome-wide association study (GWAS) for renal sinus fat was performed using an
additive model with approximately 2.5 million imputed single nucleotide
polymorphisms (SNPs). Finally, we identified the associations of renal sinus fat
in our GWAS results with validated SNPs for renal function (n=16), BMI (n=32),
and waist-to-hip ratio (WHR, n=14), and applied a multi-SNP genetic risk score
method to determine if the SNPs for each renal and obesity trait were in
aggregate associated with renal sinus fat. RESULTS: The heritability of renal
sinus fat was 39% (p<0.0001); results were not materially different after
adjustment for BMI (39%) or VAT (40%). No SNPs reached genome-wide significance
in our GWAS. In our candidate gene analysis, we observed nominal, direction
consistent associations with renal sinus fat for one SNP associated with renal
function (p=0.01), two associated with BMI (p<0.03), and two associated with WHR
(p<0.03); however, none remained significant after accounting for multiple
testing. Finally, we observed that in aggregate, the 32 SNPs associated with BMI
were nominally associated with renal sinus fat (multi-SNP genetic risk score
p=0.03). CONCLUSIONS: Renal sinus fat is a heritable trait, even after accounting
for generalized and abdominal adiposity. This provides support for further
research into the genetic determinants of renal sinus fat. While our study was
underpowered to detect genome-wide significant loci, our candidate gene BMI risk
score results suggest that variability in renal sinus fat may be associated with
SNPs previously known to be associated with generalized adiposity.
PMID- 22044752
TI - RNA editing sites exist in protein-coding genes in the chloroplast genome of
Cycas taitungensis.
AB - RNA editing is a post-transcriptional process that results in modifications of
ribonucleotides at specific locations. In land plants editing can occur in both
mitochondria and chloroplasts and most commonly involves C-to-U changes,
especially in seed plants. Using prediction and experimental determination, we
investigated RNA editing in 40 protein-coding genes from the chloroplast genome
of Cycas taitungensis. A total of 85 editing sites were identified in 25
transcripts. Comparison analysis of the published editotypes of these 25
transcripts in eight species showed that RNA editing events gradually disappear
during plant evolution. The editing in the first and third codon position
disappeared quicker than that in the second codon position. ndh genes have the
highest editing frequency while serine and proline codons were more frequently
edited than the codons of other amino acids. These results imply that retained
RNA editing sites have imbalanced distribution in genes and most of them may
function by changing protein structure or interaction. Mitochondrion protein
coding genes have three times the editing sites compared with chloroplast genes
of Cycas, most likely due to slower evolution speed.
PMID- 22044753
TI - Immunomonitoring results of a phase II/III study of malignant ascites patients
treated with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3).
AB - Patients with malignant ascites secondary to primary carcinomas benefit from
intraperitoneal therapy with the trifunctional antibody catumaxomab (anti-EpCAM *
anti-CD3). Here, we report the analysis of peritoneal fluid samples from 258
patients with malignant ascites randomized to catumaxomab or control groups to
investigate the molecular effects of catumaxomab treatment. In the catumaxomab
group, tumor cell numbers and peritoneal levels of VEGF decreased, whereas the
activation status of CD4(+) and CD8(+) T-cell populations increased more than two
fold after treatment. Notably, CD133(+)/EpCAM(+) cancer stem cells vanished from
the catumaxomab samples but not from the control samples. In vitro investigations
indicated that catumaxomab eliminated tumor cells in a manner associated with
release of proinflammatory Th1 cytokines. Together, our findings show that
catumaxomab therapy activates peritoneal T cells and eliminates EpCAM(+) tumor
cells, establishing a molecular and cellular basis to understand in vivo efficacy
within the immunosuppressed malignant ascites tissue microenvironment.
PMID- 22044754
TI - Evaluation of the efficacy of immunocastration vaccine composed of gonadotrophin
releasing hormone conjugated with Salmonella typhimurium flagellin in rats.
AB - Immunocastration is an alternative method to replace surgical castration that is
commonly performed in domestic and pet animals. In this study, a new
immunocastration vaccine was developed, and its efficacy was evaluated in male
rats. Six tandem copies of gonadotrophin-releasing hormone (GnRH) peptide were
genetically fused to Salmonella typhimurium flagellin fljB (STF2) that is a
ligand of toll-like receptor 5 (TLR5). The recombinant STF2-GnRH protein
expressed in Escherichia coli was used as the immunocastration vaccine. Sixteen
male rats were equally assigned to four groups. Excluding the control rats, three
groups were immunized with 100, 200 and 400 MUg of the STF2-GnRH vaccine,
respectively. All of the immunized rats developed significantly higher titres of
antibodies to GnRH than the control rats. The size and weight of both testes and
epididymides from the immunized rats were significantly smaller than those of the
control rats. Testicular tissues in the immunized rats demonstrated atrophy of
seminiferous tubules and decreased numbers of both spermatogonia and
spermatocytes. These data indicate that the newly developed STF2-GnRH vaccine has
a potent immunogenicity to GnRH and efficiently suppresses the development of
testes in rats.
PMID- 22044755
TI - Gene expression profiles of breast biopsies from healthy women identify a group
with claudin-low features.
AB - BACKGROUND: Increased understanding of the variability in normal breast biology
will enable us to identify mechanisms of breast cancer initiation and the origin
of different subtypes, and to better predict breast cancer risk. METHODS: Gene
expression patterns in breast biopsies from 79 healthy women referred to breast
diagnostic centers in Norway were explored by unsupervised hierarchical
clustering and supervised analyses, such as gene set enrichment analysis and gene
ontology analysis and comparison with previously published genelists and
independent datasets. RESULTS: Unsupervised hierarchical clustering identified
two separate clusters of normal breast tissue based on gene-expression profiling,
regardless of clustering algorithm and gene filtering used. Comparison of the
expression profile of the two clusters with several published gene lists
describing breast cells revealed that the samples in cluster 1 share
characteristics with stromal cells and stem cells, and to a certain degree with
mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share
many features with the newly identified claudin-low breast cancer intrinsic
subtype, which also shows characteristics of stromal and stem cells. More women
belonging to cluster 1 have a family history of breast cancer and there is a
slight overrepresentation of nulliparous women in cluster 1. Similar findings
were seen in a separate dataset consisting of histologically normal tissue from
both breasts harboring breast cancer and from mammoplasty reductions. CONCLUSION:
This is the first study to explore the variability of gene expression patterns in
whole biopsies from normal breasts and identified distinct subtypes of normal
breast tissue. Further studies are needed to determine the specific cell
contribution to the variation in the biology of normal breasts, how the clusters
identified relate to breast cancer risk and their possible link to the origin of
the different molecular subtypes of breast cancer.
PMID- 22044756
TI - BDM1, a phosducin-like gene of Fusarium graminearum, is involved in virulence
during infection of wheat and maize.
AB - Fusarium graminearum is a common pathogen of wheat and maize throughout the
world. Despite recent advances in the elucidation of the genetic basis of
virulence, significant gaps in the regulatory network underlying pathogenesis
remain to be filled. In particular, little is known at the molecular level about
the overlap among mechanisms of pathogenicity on maize and wheat. G-protein
signalling has been implicated in pathogenesis in F. graminearum, although the
underlying mechanisms are not fully understood. In this study, we investigated
the involvement of a putative phosducin-like gene (BDM1) in growth, development
and pathogenesis in F. graminearum. Targeted deletion of BDM1 revealed roles in
sexual and asexual sporulation, germ tube development, hyphal branching and
mycelial morphology. During pathogenesis, BDM1 is required for wild-type levels
of colonization of maize silk tissue and stalks, but is dispensable for the
colonization of kernels. The deletion of BDM1 also reduced the virulence of F.
graminearum during the infection of wheat seedlings and heads, resulting in a
significant reduction in fungal biomass and a delayed spread of visual symptom
expression (i.e. bleaching in heads). Furthermore, BDM1 is required for wild-type
levels of deoxynivalenol biosynthesis during the infection of wheat heads and
maize silks. In summation, BDM1 is one of the few genes characterized to date in
F. graminearum involved in virulence during infection of both maize and wheat.
Thus, the functional characterization of BDM1 has established a new regulatory
link between pathogenesis in maize and wheat, and provides a genetic resource
through which the regulatory networks underlying virulence in F. graminearum can
be further elucidated.
PMID- 22044757
TI - Plasma membrane association of three classes of bacterial toxins is mediated by a
basic-hydrophobic motif.
AB - Plasma membrane targeting is essential for the proper function of many bacterial
toxins. A conserved fourhelical bundle membrane localization domain (4HBM) was
recently identified within three diverse families of toxins: clostridial
glucosylating toxins, MARTX toxins and Pasteurella multocida-like toxins. When
expressed in tissue culture cells or in yeast, GFP fusions to at least one 4HBM
from each toxin family show significant peripheral membrane localization but with
differing profiles. Both in vivo expression and in vitro binding studies reveal
that the ability of these domains to localize to the plasma membrane and bind
negatively charged phospholipids requires a basic-hydrophobic motif formed by the
L1 and L3 loops. The different binding capacity of each 4HBM is defined by the
hydrophobicity of an exposed residue within the motif. This study establishes
that bacterial effectors utilize a normal host cell mechanism to locate the
plasma membrane where they can then access their intracellular targets.
PMID- 22044758
TI - Mandibular flexure and its significance on implant fixed prostheses: a review.
AB - PURPOSE: The aims of this review are to determine the effect of mandibular
flexure on the "implant-framework system," and analyze the existing literature on
the topic. MATERIALS AND METHODS: A MEDLINE and PubMed search was conducted to
identify any articles in English related to the topic published up to May 2010
using the search words "mandible,""dental implants,""dental impression
technique,""jaw movement,""dental stress analysis," and "mechanical stress."
RESULTS: The search identified 40 and 36 articles from MEDLINE and PubMed,
respectively. Twenty articles met the inclusion criteria. CONCLUSIONS: Mandibular
flexure is a multifactorial phenomenon, and the effect of the implant-framework
system in this is unclear. Studies have focused mainly on the fully edentulous
mandible. These have found that mandibular flexure should be taken into
consideration when designing a prosthesis and have suggested that dividing the
prosthesis at the symphysis region, or into multiple implant fixed dental
prostheses, may minimize the effect of mandibular flexure on the implant
prosthesis. At this time, no studies have investigated the effect of mandibular
flexure on long-span, unilateral, implant fixed prostheses. The clinical
significance of mandibular flexure on the success of dental implant treatment is
at this time unclear, and further research is needed.
PMID- 22044759
TI - Current trends in the diagnosis and treatment of autoimmune hepatitis in Japan.
AB - While a certain international consensus has been reached regarding the diagnosis
and treatment of autoimmune hepatitis (AIH), there are some unique clinical
characteristics of AIH in Japan. For diagnosis of AIH using the new simplified
criteria proposed by the International Autoimmune Hepatitis Group, it is
necessary to re-evaluate the antibody titer determined by using HEp-2 cells,
which are widely used in Japan, and the finding of emperipolesis in liver
histology, although the criteria are useful for rapid identification of AIH in
routine clinical practice. The use of azathioprine as first-line therapy for AIH
is limited in Japan because the drug is not covered by the Japanese national
health insurance. Concomitant use of ursodeoxycholic acid (UDCA) to reduce
corticosteroids and use of UDCA as monotherapy are therefore considered
promising. Moreover, a relatively good survival rate has been reported in
patients who developed AIH-induced acute liver failure and underwent living-donor
liver transplantation. Current trends in the diagnosis and treatment of AIH in
Japan are described in this report with a review of recent findings.
PMID- 22044760
TI - CD68 and CD163 as prognostic factors for Korean patients with Hodgkin lymphoma.
AB - BACKGROUND: Limited progress had been made in prognostic stratification of
patients with Hodgkin lymphoma (HL) until recent studies suggested that the
number of CD68-expressing macrophages is prognostic in classical HL. However, its
significance in Asian patients with HL has not been explored yet perhaps because
of its low incidence in Asia. METHODS: In this work, we performed
immunohistochemical analysis of CD163, as well as CD68, in 144 Korean patients
with HL treated between November 1990 and December 2009 in a single center. The
relative percentages of CD68+ and CD163+ cells with respect to the overall
cellularity (CD68 index and CD163 index, respectively) were correlated with
clinical outcomes. RESULTS: Both high CD68 and CD163 indices (>20%) were
associated with a rise in treatment-related deaths and poorer event-free survival
(P = 0.009 and P = 0.0023, respectively), disease-specific survival (P = 0.011
and P = 0.001), and overall survival (P = 0.023 and P = 0.001). In particular, a
high CD163 index was related to lower complete response (CR) rate (P = 0.022) and
shorter duration of CR (P = 0.030). CONCLUSIONS: High index of either CD68 or
CD163 (>20%) is significantly correlated with poor prognosis in Korean patients
with HL. CD163, a specific marker of macrophages, seems to be another prognostic
factor for classical HL.
PMID- 22044761
TI - Does haemophilia protect against ischaemic cardiovascular disease?
PMID- 22044762
TI - Transforming care at the bedside for nurse faculty: can continuous quality
improvement transform nursing education?
PMID- 22044764
TI - Evidence for behavioral benefits of early dietary supplementation with
CoEnzymeQ10 in a slowly progressing mouse model of Huntington's disease.
AB - Controversies surround the usefulness of Coenzyme Q10 (CoQ10) in Huntington's
disease (HD), an autosomal dominant, fatal, neurodegenerative disease with no
cure or disease modifying treatment. CoQ10, an endogenous substrate for electron
transport and an anti-oxidant, has been shown in some but not all studies to
improve symptoms and survival in mouse models of HD. Previous studies have been
conducted in fast-progressing models that better mimic the juvenile forms of HD
than the much more common middle-age onset form, possibly accounting for mixed
results. Establishing the usefulness of CoQ10 to alter HD disease course in a
model that better recapitulates the progressive features of the human disorder is
important because clinical trials of CoQ10, which is safe and well tolerated, are
being planned in patients. The CAG140 knock-in (KI) mouse model of HD in which an
expanded (approximately 120) CAG repeat is inserted in the mouse gene provides a
model of the mutation in the proper genomic and protein context. These mice
display progressive motor, cognitive and emotional anomalies, transcriptional
disturbances and late striatal degeneration. Homozygote mutant CAG140 KI mice and
wild-type littermates were fed CoQ10 (0.2%, 0.6%) in chow, and behavioral and
pathological markers of disease were examined. CoQ10 improved early behavioral
deficits and normalized some transcriptional deficits without altering huntingtin
aggregates in striatum. The lower dose (0.2%) was more beneficial than 0.6%.
Similar to previous studies, this low dose also induced deleterious effects in
open field and rotarod in WT mice, however these effects are of unclear clinical
significance in view of the excellent safety profile of CoQ10 in humans. These
data confirm that CoQ10 may be beneficial in HD but suggest that maximum benefit
may be observed when treatment is begun at early stages of the disease and that
dosage may be critical.
PMID- 22044766
TI - Diagnostic utility and clinical usefulness of the pocket echocardiographic
device.
AB - BACKGROUND: The pocket echocardiograph (PE) with color Doppler imaging belongs to
a new class of diagnostic tools, the feasibility and accuracy of which is not
well established. The aim of this study was to assess the feasibility and
diagnostic value of transthoracic echocardiography (TTE) performed with the use
of PE by a cardiology resident (2nd year of training) and by an experienced
cardiologist. METHODS: The study population comprised 220 consecutive patients
(142 men, mean age 63 +/- 8 years), 110 of whom were admitted to our intensive
cardiac care unit (ICU) and 110 patients referred for TTE from the outpatient
clinic. All patients had PE TTE performed by a resident (60 ICU patients, 60
outpatients) or a cardiologist (50 ICU patients, 50 outpatients). Within 24 h of
PE TTE, all subjects had a standard TTE (sTTE) performed by an experienced
echocardiographer. RESULTS: 96% of patients had echocardiographic measurements
completed by both PE TTE and sTTE. The dimensions measured with PE TTE by the
resident and the cardiologist showed good to excellent correlation with sTTE (r =
0.64-0.96, P < 0.001). The agreement in detection of various pathologies between
PE TTE performed by the resident and sTTE examinations was moderate to very good,
whereas it was good to excellent if PE TTE was performed by the experienced
cardiologist. CONCLUSION: The diagnostic accuracy of the PE in basic assessment
of cardiac morphology and function as compared to standard echocardiography is
moderate to very good for a cardiology resident and good to excellent for an
experienced cardiologist. (Echocardiography 2012;29:1-6).
PMID- 22044765
TI - Rbfox proteins regulate alternative splicing of neuronal sodium channel SCN8A.
AB - The SCN8A gene encodes the voltage-gated sodium channel Na(v)1.6, a major channel
in neurons of the CNS and PNS. SCN8A contains two alternative exons,18N and 18A,
that exhibit tissue specific splicing. In brain, the major SCN8A transcript
contains exon 18A and encodes the full-length sodium channel. In other tissues,
the major transcript contains exon 18N and encodes a truncated protein, due to
the presence of an in-frame stop codon. Selection of exon 18A is therefore
essential for generation of a functional channel protein, but the proteins
involved in this selection have not been identified. Using a 2.6 kb Scn8a
minigene containing exons 18N and 18A, we demonstrate that co-transfection with
Fox-1 or Fox-2 initiates inclusion of exon 18A. This effect is dependent on the
consensus Fox binding site located 28 bp downstream of exon 18A. We examined the
alternative splicing of human SCN8A and found that the postnatal switch to exon
18A is completed later than 10 months of age. In purified cell populations,
transcripts containing exon 18A predominate in neurons but are not present in
oligodendrocytes or astrocytes. Transcripts containing exon 18N appear to be
degraded by nonsense-mediated decay in HEK cells. Our data indicate that RBFOX
proteins contribute to the cell-specific expression of Na(v)1.6 channels in
mature neurons.
PMID- 22044767
TI - The development of service users in the provision of verbal feedback to student
nurses in a clinical simulation environment.
AB - The School of Nursing and Midwifery at Robert Gordon University, Aberdeen, has a
sustained history of working in partnership with service users in their role as
patient volunteers. The patient volunteers make a pivotal contribution towards
the delivery of clinical skills as "real" patients. They work within a scenario
context, overseen and facilitated by academic staff. Evaluations have identified
that the patient volunteers find this experience rewarding, worthwhile and a way
of contributing to the education of student nurses. Whilst this is already a
successful element of the student's learning, staff were cognisant of the need to
develop this aspect further. A case study approach was adopted to review the
experience of the patient volunteers in their provision of feedback to students.
In accordance with the evidence base, it was proposed to enhance the volunteer
patient's role in providing verbal face to face feedback to students. An
educational package for the patient volunteers was developed and a current
simulation event within the curriculum was identified that would allow the
volunteers to practice giving feedback. This was then evaluated and following
ethical approval, a series of focus groups were undertaken with the patient
volunteers. The data collected identified the strengths and limitations of this
experience and as a result of this an implementation plan was identified aimed at
enhancing the patient volunteer's and the student's experience.
PMID- 22044768
TI - Repeated exposure of adult rats to Aroclor 1254 induces neuronal injury and
impairs the neurochemical manifestations of the NMDA receptor-mediated
intracellular signaling in the hippocampus.
AB - Aroclor 1254 is a mixture of polychlorinated biphenyls (PCBs), a class of
environmental toxins which cause a wide spectrum of neurotoxic effects. Learning
and memory deficits are the profound effects of PCBs which may be related to
hippocampal dysfunction. To get insight into the underlying neurochemical
mechanisms, we employed the microdialysis technique to investigate the effect of
repeated exposure of adult male Wistar rats to Aroclor 1254 (10mg/kg b.w., daily,
ig., for 14days), on the neurochemical parameters of NMDA receptor-mediated
glutamatergic signaling in the hippocampus in vivo assessed using the
microdialysis technique. The results demonstrated that exposure to Aroclor 1254,
which was associated with substantial neuronal damage and loss in the
hippocampus, markedly decreased the NMDA-induced extracellular accumulation of
newly loaded (45)CaCl(2), cGMP and glutamate, and reduced the basal content of
the NO precursor, arginine, indicating inhibition of the NMDA/NO/cGMP pathway.
Aroclor 1254 exposure also decreased the basal microdialysate content of
glutamate and glutamine, which may cause inadequate supply of the
neurotransmitter glutamate, while the level of two other neuroactive amino acids,
aspartate or taurine was not affected by the exposure. The results underscore
neuronal lesion and inhibition of NMDA receptor-mediated glutamatergic signaling
in hippocampus as a potential major contributor to the cognitive deficits
associated with exposure to PCB.
PMID- 22044769
TI - Expression, purification of herpes simplex virus type 1 US11 protein, and
production of US11 polyclonal antibody.
AB - BACKGROUND: The US11 protein of herpes simplex virus type 1 (HSV-1) is a small,
highly basic phosphoprotein expressed at late times during infection. To date,
the function of US11 protein in cell culture and animal models is poorly
understood. To further investigate the function of the US11 protein, this study
was undertaken to express the US11 protein and raise a polyclonal antibody.
RESULTS: The US11 gene was cloned into the prokaryotic expression vector pET-32a
(+) to express His-tagged US11 protein in Escherichia coli. After purification by
nickel affinity chromatography and refolding, the recombinant protein was used to
raise the anti-US11 polyclonal antibody. Western blot analysis demonstrated that
the US11 protein was specifically recognized by the polyclonal antibody, and
immunofluorescent assay also showed that the antibody was able to probe the US11
protein in the cells infected with HSV-1. CONCLUSIONS: In the present study, we
obtained a high-level expression of the recombinant US11 protein as well as high
titers of rabbit polyclonal antibody specially against US11 protein in HSV-1
infected cells. This special polyclonal antibody provides a good tool for further
studying structural and functional characterization of HSV-1 US11 protein.
PMID- 22044770
TI - Secondhand smoke exposure induces Raf/ERK/MAPK-mediated upregulation of
cerebrovascular endothelin ETA receptors.
AB - BACKGROUND: Cigarette smoking enhances the risk of stroke. However, the
underlying molecular mechanisms are largely unknown. The present study
established an in vivo rat secondhand cigarette smoking (SHS) model and examined
the hypothesis that SHS upregulates endothelin receptors with increased
cerebrovascular contraction via the Raf/extracellular signal-regulated kinase
(ERK)/mitogen-activated protein kinases (MAPK) pathway. RESULTS: Rats were
exposed to SHS for up to 8 weeks. The cerebral artery vasoconstriction was
recorded by a sensitive myograph. The mRNA and protein expressions for endothelin
receptors in cerebral arteries were studied by real-time PCR and Western blot.
Compared to fresh air exposed rats, cerebral arteries from SHS rats exhibited
stronger contractile responses (P < 0.05) mediated by endothelin type A (ETA)
receptors. The expressions of mRNA and protein for ETA receptors in the cerebral
arteries from SHS rats were higher (P < 0.05) than that in control. SHS did not
affect endothelin type B (ETB) receptor-mediated contractions, mRNA or protein
levels. The results suggest that SHS upregulates ETA, but not ETB receptors in
vivo. After SHS exposure, the mRNA levels of Raf-1 and ERK1/2, the protein
expression of phosphorylated (p)-Raf-1 and p-ERK1/2 were increased (P < 0.05).
Raf-1 inhibitor, GW5074 suppressed the enhanced ETA receptor-mediated
contraction, mRNA and protein levels induced by SHS. In addition, GW5074
inhibited the SHS-caused increased mRNA and phosphorylated protein levels of Raf
1 and ERK1/2, suggesting that SHS induces activation of the Raf/ERK/MAPK pathway.
CONCLUSIONS: SHS upregulates cerebrovascular ETA receptors via the Raf/ERK/MAPK
pathway, which provides novel understanding of mechanisms involved in SHS
associated stroke.
PMID- 22044771
TI - Simultaneous cell growth and ethanol production from cellulose by an engineered
yeast consortium displaying a functional mini-cellulosome.
AB - BACKGROUND: The recalcitrant nature of cellulosic materials and the high cost of
enzymes required for efficient hydrolysis are the major impeding steps to their
practical usage for ethanol production. Ideally, a recombinant microorganism,
possessing the capability to utilize cellulose for simultaneous growth and
ethanol production, is of great interest. We have reported recently the use of a
yeast consortium for the functional presentation of a mini-cellulosome structure
onto the yeast surface by exploiting the specific interaction of different
cohesin-dockerin pairs. In this study, we engineered a yeast consortium capable
of displaying a functional mini-cellulosome for the simultaneous growth and
ethanol production on phosphoric acid swollen cellulose (PASC). RESULTS: A yeast
consortium composed of four different populations was engineered to display a
functional mini-cellulosome containing an endoglucanase, an exoglucanase and a
beta-glucosidase. The resulting consortium was demonstrated to utilize PASC for
growth and ethanol production. The final ethanol production of 1.25 g/L
corresponded to 87% of the theoretical value and was 3-fold higher than a similar
yeast consortium secreting only the three cellulases. Quantitative PCR was used
to enumerate the dynamics of each individual yeast population for the two
consortia. Results indicated that the slight difference in cell growth cannot
explain the 3-fold increase in PASC hydrolysis and ethanol production. Instead,
the substantial increase in ethanol production is consistent with the reported
synergistic effect on cellulose hydrolysis using the displayed mini-cellulosome.
CONCLUSIONS: This report represents a significant step towards the goal of
cellulosic ethanol production. This engineered yeast consortium displaying a
functional mini-cellulosome demonstrated not only the ability to grow on the
released sugars from PASC but also a 3-fold higher ethanol production than a
similar yeast consortium secreting only the three cellulases. The use of more
complex cellulosomal structures may further improve the overall efficiency for
ethanol production.
PMID- 22044772
TI - Non-invasive assessment of liver fibrosis in patients after the Fontan operation.
AB - BACKGROUND: This study analyzed the change in liver fibrosis markers after the
Fontan operation and investigated their clinical usefulness as an index of
congestive liver fibrosis. METHODS: The study enrolled 24 patients who underwent
the Fontan operation between January 1994 and December 2008. We subdivided the
postoperative period into four intervals and then compared the hepatological
markers during each. Eighteen patients underwent postoperative cardiac
catheterization and the correlation between hepatological markers and the
inferior vena cava (IVC) pressure was analyzed. RESULTS: The mean age of the
patients was 138.6 months and the mean interval between the Fontan operation and
the examination was 97.8 months. Type IV collagen was extremely high in every
interval (I, 286 +/- 93; II, 265 +/- 93; III, 305 +/- 143; IV, 206 +/- 70), while
none of the laboratory variables changed significantly in each interval. A
significant positive correlation was observed between type IV collagen and the
IVC pressure, but no significant correlation with any other hepatological marker
was detected. CONCLUSIONS: No specific parameter that reflects the progress in
liver fibrosis was identified in this study. The possibility exists that type IV
collagen reflects the degree of hepatic congestion.
PMID- 22044773
TI - Polymerization profile analysis of resin composite dental restorative materials
in real time.
AB - OBJECTIVES: In this study, the hypothesis that the polymerization shrinkage
profile of "low shrinkage" non-methacrylate based composite; Silorane and "low
shrinkage" high molecular mass methacrylate based composite; Kalore is not
different from that of three conventional methacrylate based composites (Gradia
Direct X, Filtek Supreme XT and Beautifil II) was tested. METHODS: Five
commercially available composites were analysed: one "low shrinkage" non
methacrylate based composite (Silorane); one "low shrinkage" high molecular mass
methacrylate based composite (Kalore) and three conventional methacrylate based
composites (Gradia Direct X, Filtek Supreme XT and Beautifil II). Polymerization
shrinkage was measured using an electromagnetic balance which recorded changes in
composite buoyancy occurring due to volumetric changes during polymerization.
This instrument allowed real time volumetric shrinkage measurements to be made at
40 ms intervals. RESULTS: All five resin composites demonstrated a similar
volumetric shrinkage profile during polymerization. The rate of shrinkage of all
five composites decreased from t=0 at a rate approximating x=t. After 170 s the
rate of shrinkage of all five composites was at or below 0.01%/s. During the
initial 5s of light exposure Silorane and Kalore exhibited a significantly lower
(p<0.05) rate of contraction relative to the three conventional methacrylate
composites. After 640 s of analysis, Silorane exhibited a significantly lower
(p<0.05) percentage volumetric contraction compared to the other four analysed
materials. CONCLUSIONS: The newly developed "low shrinkage" composites (Silorane,
Kalore) in the present study demonstrated significantly lower (p<0.05) shrinkage
rates and shrinkage volumes compared to the three conventional methacrylate
composites. Investigation to identify whether polymerization shrinkage profile
analysis is a good predictor of relative polymerization contraction stress levels
generated by different composites, is warranted. CLINICAL SIGNIFICANCE:
Clinicians making a resin composite selection with the view to minimizing the
clinical effects of polymerization shrinkage must consider the rate of
polymerization as well as the total volumetric shrinkage of a composite. Silorane
(non methacrylate composite) and Kalore (high molecular mass methacrylate
composite) have the ability to exhibit lower shrinkage rates and lower shrinkage
volumes compared to conventional methacrylate composites.
PMID- 22044774
TI - Colour stability of relined dentures after chemical disinfection. A randomised
clinical trial.
AB - BACKGROUND: This randomised clinical study evaluated the effect of chemical
disinfection with sodium perborate or chlorhexidine on the colour stability of a
hard chairside reline resin during six months. METHODS: Hard chairside reline
resin (Tokuyama Rebase Fast II) was used to reline complete dentures. After
baseline colour measurements, the patients were randomly divided into 3 groups (n
= 15) and allocation was concealed with the use of the BioStat program. The
dentures were cleansed according to three methods: CG (control group)--brushing
with coconut soap and soft toothbrush, PG (Perborate group)--brushing according
to previous methods and disinfection with warmed sodium perborate solution
(Corega Tabs) for 5 min, once a day for 6 months and ChxG (Chlorhexidine Group)-
brushing according to CG and disinfection with chlorhexidine digluconate 2% for
5min once a day for 6 months. The data of DeltaE*, DeltaL*, Deltaa* and Deltab*
were analysed by 2-way repeated-measures ANOVAs and Tukey tests (alpha = 0.05).
RESULTS: There were significant differences amongst groups for DeltaL, Deltaa and
Deltab. The time had a significant effect on DeltaE and DeltaL, for all groups
evaluated. CONCLUSION: Changes in some colour parameters (DeltaL, Deltaa and
Deltab) of the reline resin Tokuyama Rebase were observed when the dentures were
disinfected by perborate and chlorhexidine digluconate 2% solutions. The colour
stability of was also influenced by time, regardless of disinfection or
nondisinfection. CLINICAL IMPLICATIONS: Colour stability of the denture materials
is one variable to be considered when choosing disinfection methods. The data in
this study will be useful to clinicians when they are selecting disinfectant
solutions for disinfection of relined denture.
PMID- 22044775
TI - Results of combined treatment of anaplastic thyroid carcinoma (ATC).
AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive human
malignancies. It is associated with a high rate of local recurrence and with poor
prognosis. METHODS: We retrospectively reviewed 44 consecutive patients treated
between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined
treatment strategy derived from the one developed at the Institut Gustave Roussy
included total thyroidectomy and cervical lymph-node dissection, when feasible,
combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W,
hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper
mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin. RESULTS:
Thirty-five patients received the three-phase combined treatment. Complete
response after treatment was achieved in 14/44 patients (31.8%). Eight patients
had a partial response (18.2%). Twenty-two (50%) had progressive disease. All
patients with metastases at diagnosis died shortly afterwards. Thirteen patients
are still alive. The median survival of the entire population was 8 months.
CONCLUSION: Despite the ultimately dismal prognosis of ATC, multimodality
treatment significantly improves local control and appears to afford long-term
survival in some patients. There is active ongoing research, and results obtained
with new targeted systemic treatment appear encouraging.
PMID- 22044776
TI - Efficient and selective removal of chloroacetyl group promoted with tetra-n
butylammonium fluoride (TBAF).
AB - A practical method for the efficient and selective cleavage of chloroacetyl
protecting group using tetra-n-butylammonium fluoride (TBAF) in THF solution at
rt was disclosed.
PMID- 22044777
TI - Mental illness related disparities in diabetes prevalence, quality of care and
outcomes: a population-based longitudinal study.
AB - BACKGROUND: Health care disparity is a public health challenge. We compared the
prevalence of diabetes, quality of care and outcomes between mental health
clients (MHCs) and non-MHCs. METHODS: This was a population-based longitudinal
study of 139,208 MHCs and 294,180 matched non-MHCs in Western Australia (WA) from
1990 to 2006, using linked data of mental health registry, electoral roll
registrations, hospital admissions, emergency department attendances, deaths, and
Medicare and pharmaceutical benefits claims. Diabetes was identified from
hospital diagnoses, prescriptions and diabetes-specific primary care claims
(17,045 MHCs, 26,626 non-MHCs). Both univariate and multivariate analyses
adjusted for socio-demographic factors and case mix were performed to compare the
outcome measures among MHCs, category of mental disorders and non-MHCs. RESULTS:
The prevalence of diabetes was significantly higher in MHCs than in non-MHCs
(crude age-sex-standardised point-prevalence of diabetes on 30 June 2006 in those
aged >=20 years, 9.3% vs 6.1%, respectively, P < 0.001; adjusted odds ratio (OR)
1.40, 95% CI 1.36 to 1.43). Receipt of recommended pathology tests (HbA1c,
microalbuminuria, blood lipids) was suboptimal in both groups, but was lower in
MHCs (for all tests combined; adjusted OR 0.81, 95% CI 0.78 to 0.85, at one year;
and adjusted rate ratio (RR) 0.86, 95% CI 0.84 to 0.88, during the study period).
MHCs also had increased risks of hospitalisation for diabetes complications
(adjusted RR 1.20, 95% CI 1.17 to 1.24), diabetes-related mortality (1.43, 1.35
to 1.52) and all-cause mortality (1.47, 1.42 to 1.53). The disparities were most
marked for alcohol/drug disorders, schizophrenia, affective disorders, other
psychoses and personality disorders. CONCLUSIONS: MHCs warrant special attention
for primary and secondary prevention of diabetes, especially at the primary care
level.
PMID- 22044778
TI - Characterization of three homoeologous cDNAs encoding chloroplast-targeted
aminolevulinic acid dehydratase in common wheat.
AB - In the tetrapyrrole biosynthetic pathway of higher plants, 5-aminolevulinic acid
(ALA) is metabolized by ALA dehydratase (ALAD). Here, we isolated ALAD1 cDNA from
common wheat (Triticum aestivum L.) and its diploid progenitors, and produced
transgenic tobacco plants expressing the wheat ALAD1 gene. The ALAD1 genes were
highly conserved among wheat relatives, and three homoeologous loci of wheat
ALAD1 (TaALAD1) were equally transcribed in common wheat. A transient expression
assay of a TaALAD1-GFP (green fluorescent protein) fusion protein suggested that
TaALAD1 is localized in chloroplasts. Overexpression of TaALAD1 in transgenic
tobacco resulted in a significant increase in ALAD activity in leaves. Moreover,
the transgenic tobacco showed vigorous growth and increased survival rate on
medium containing ALA at herbicidal concentrations. These results indicate that
wheat ALAD1 has catalytic activity in metabolizing ALA in plastids, and that
ectopic expression of TaALAD1 in transgenic plants increases their tolerance to
ALA application at high concentrations.
PMID- 22044779
TI - Family physician attitudes in managing obesity: a cross-sectional survey study.
AB - BACKGROUND: Obesity is epidemic in primary care. While family physicians care for
the consequences of obesity, they do not generally feel confident managing
obesity itself. We examined the barriers to obesity management in a sample of
family physicians in a primary care practice-based research network (PBRN).
FINDINGS: 204 family physicians were invited to respond to a survey on physician
beliefs about obese patients and causes of obesity. A total of 75 physicians
responded to the survey. Responses were factor analyzed using standard
techniques. Comments were sorted into ranked themes by the investigators. The
results show systemic barriers to obesity management. Seven general factors were
identified, with some discrepancy seen in the role of "psychobehavioral
causation" between rural and non-rural physicians. Themes derived from the
comments reflected frustration with the resources and structure of current
primary care systems to be able to deal with obesity. CONCLUSIONS: Our pilot
survey suggests that differences in beliefs regarding the causes of obesity may
exist between rural and non-rural physicians. Further research in larger, more
diverse samples is necessary to further illuminate practice differences. More
comprehensive approaches to obesity management, like the Chronic Care Model, are
suggested by these results.
PMID- 22044780
TI - Subversion of innate immune responses by bacterial hindrance of NF-kappaB
pathway.
AB - Bacterial infections cause substantial mortality and burden of disease globally.
Induction of a strong innate inflammatory response is the first common host
mechanism required for elimination of the invading pathogens. The host
transcription factor, nuclear factor kappa B (NF-kappaB) is essential for immune
activation. Conversely, bacterial pathogens have evolved strategies to interfere
directly with host cell signalling by regulating or mimicking host proteins.
Given the key role of NF-kappaB in the host inflammatory response, bacteria have
expectedly developed virulence effectors interfering with NF-kappaB signalling
pathways. In this review, we explore the bacterial mechanisms utilized to prevent
effective NF-kappaB signalling, which in turn usurp the host inflammatory
response.
PMID- 22044781
TI - Impact of heteroresistance to colistin in meningitis caused by Acinetobacter
baumannii.
PMID- 22044782
TI - Acute appendicitis, a rare complication of varicella: a report of three cases.
AB - Acute appendicitis is a very rare complication of varicella, and is rarely
reported in studies of complications of varicella or appendicitis. This report
describes three cases of acute appendicitis in the course of varicella, diagnosed
in Clinical Department of Infectious Diseases at Split University Hospital,
Croatia between 1998 and 2010. Varicella was diagnosed clinically, and in two
cases confirmed by positive serological tests for varicella-zoster virus (VZV).
In addition to routine histopathological examination, testing for viral antigens
or DNA in the appendix, omentum and peripheral blood by genetic and
immunohistochemistry methods may be important to confirm whether VZV and
appendicitis are etiopathogenetically connected.
PMID- 22044783
TI - effect of embryonic genotype on reference gene selection for RT-qPCR
normalization.
AB - To obtain more reliable results with biological significance, it requires data
normalization using an appropriate internal control gene. In rabbits, there are
classic stable reference genes that have been identified for normalization in
oocytes and pre-implantation stage embryos. However, effects of embryonic
genotype on reference gene selection have not been elucidated. The aim of this
study was to test (i) the stability of mRNA transcription level for histone
(H2afz) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes in rabbit
blastocysts from two lines selected by different criteria (litter size and post
weaning daily weight gain) and (ii) its influence on biological significance
examined by means of a set of embryonic transcripts, such as POU5F1 (Oct-4),
epidermal growth factor receptor (erbB3), transforming growth factor-beta2,
vascular endothelial growth factor and gamma interferon (Ifn-gamma). The geNorm,
NormFinder and BestKeeper programs showed similar results, pointing out that
H2afz and GAPDH were the most stable reference genes in rabbits selected on
litter size at weaning. Moreover, our study revealed that embryonic genotype
affected target gene expression when a single reference gene was used to analyse
mRNA expression in blastocysts. Results showed that GAPDH gene is better than
H2afz for gene expression studies of both embryo genotypes. A normalization
factor derived from H2afz and GAPDH is likely to be appropriate when RT-qPCR was
performed in rabbit embryos with different genotypes.
PMID- 22044784
TI - Sewer pipe, wire, epoxy, and finger tapping: the start of fMRI at the Medical
College of Wisconsin.
AB - In 1991, the Biophysics Research Institute at the Medical College of Wisconsin
was among the first groups to develop functional Magnetic Resonance Imaging
(fMRI). Our story is unique on a few levels: We didn't have knowledge of the
ability to image human brain activation with MRI using blood oxygenation
dependent (BOLD) contrast until early August of 1991 when we attended the Society
for Magnetic Resonance in Medicine (SMRM) meeting in San Francisco, yet we
produced our first BOLD-based maps of motor cortex activation about a month
later. The effort started with two graduate students, Eric Wong and myself. Only
a few days prior to that extremely important SMRM meeting, we had developed human
echo planar imaging (EPI) capability in-house. Wong designed, built, and
interfaced a head gradient coil made out of sewer pipe, wire, and epoxy to a
standard GE 1.5T MRI scanner. Also, a few months prior to building this human
head gradient coil he developed the EPI pulse sequences and image reconstruction.
All of these efforts were towards a different goal--for demonstration of Wong's
novel approach to perfusion imaging in the human brain. Following SMRM, where a
plenary lecture by Tom Brady from MGH opened our eyes to human brain activation
imaging using BOLD contrast, and where we learned that EPI was extremely helpful
if not critical to its success, we worked quickly to achieve our first results on
September 14, 1991. The story is also unique in that Jim Hyde had set up the
Biophysics Research Institute to be optimal for just this type of rapidly
advancing basic technology research. It was well equipped for hardware
development, had open and dynamic collaborative relationships with other
departments, hospitals on campus, and GE, and had a relatively flat hierarchy and
relaxed, flexible, collegial atmosphere internally. Since these first brain
activation results, MCW Biophysics has continued to be at the forefront of
functional MRI innovation, having helped to pioneer real time fMRI, high
resolution fMRI, and functional connectivity mapping.
PMID- 22044785
TI - Secretomics identifies Fusarium graminearum proteins involved in the interaction
with barley and wheat.
AB - Fusarium graminearum is a phytopathogenic fungus primarily infecting small grain
cereals, including barley and wheat. Secreted enzymes play important roles in the
pathogenicity of many fungi. In order to access the secretome of F. graminearum,
the fungus was grown in liquid culture with barley or wheat flour as the sole
nutrient source to mimic the host-pathogen interaction. A gel-based proteomics
approach was employed to identify the proteins secreted into the culture medium.
Sixty-nine unique fungal proteins were identified in 154 protein spots, including
enzymes involved in the degradation of cell walls, starch and proteins. Of these
proteins, 35% had not been identified in previous in planta or in vitro studies,
70% were predicted to contain signal peptides and a further 16% may be secreted
in a nonclassical manner. Proteins identified in the 72 spots showing
differential appearance between wheat and barley flour medium were mainly
involved in fungal cell wall remodelling and the degradation of plant cell walls,
starch and proteins. The in planta expression of corresponding F. graminearum
genes was confirmed by quantitative reverse transcriptase-polymerase chain
reaction in barley and wheat spikelets harvested at 2-6 days after inoculation.
In addition, a clear difference in the accumulation of fungal biomass and the
extent of fungal-induced proteolysis of plant beta-amylase was observed in barley
and wheat. The present study considerably expands the current database of F.
graminearum secreted proteins which may be involved in Fusarium head blight.
PMID- 22044786
TI - 5-fluorouracil arterial infusion + interferon therapy for highly advanced
hepatocellular carcinoma: A multicenter, randomized, phase II study.
AB - AIM: The efficacy and safety of 5-fluorouracil arterial infusion + interferon
therapy (FAIT) was evaluated in patients with hepatocellular carcinoma (HCC) with
a high degree of vascular invasion associated with poor prognosis, using best
salvage therapy (BST) as a reference group. METHODS: Sixty-nine patients with
advanced HCC with a high degree of vascular invasion (Vp3, Vp4, Vv3) were
randomly assigned to a FAIT group or a BST group. The FAIT group received
interferon-alpha and 5-fluorouracil combination therapy; the BST group received
either combination therapy of cisplatin and 5-fluorouracil (low-dose FP therapy)
or cisplatin for arterial infusion. RESULTS: Thirty patients in the FAIT group
and 31 patients in the BST group were included in the efficacy analysis. The
response rate (primary endpoint) was 26.7% (eight out of 30 patients) for the
FAIT group and 25.8% (eight out of 31) for the BST group. The number of
occurrences of adverse events of grade 3 or higher was 115 in 30 patients in the
FAIT group and 113 in 29 patients in the BST group. None of the deaths were
related to the study therapy. CONCLUSIONS: FAIT exerts modest antitumor effects
and poses no particular safety concerns. FAIT may be a strategy of choice worth
trying for advanced HCC with high degree of vascular invasion, which is
associated with poor prognosis.
PMID- 22044787
TI - The use of virtual reality for episodic memory assessment: effects of active
navigation.
AB - Episodic memory was assessed using Virtual Reality (VR). Forty-four (44) subjects
visualized a target virtual apartment containing specific objects in each room.
Then they visualized a second virtual apartment comprised of specific objects and
objects shared by the two apartments. Subjects navigated in the virtual
apartments in one of the following two conditions: active and passive. Four main
episodic memory components were scored from the VR exposures: (1) learning
effect; (2) active forgetting effect; (3) strategies at encoding and at
retrieval; and (4) false recognitions (FRs). The effect of navigation mode
(active vs. passive) on each memory component was examined. Active subjects had
better learning and retrieval (recognition hits) performances compared to passive
subjects. A beneficial effect of active navigation was also observed on the
source-based FR rates. Active subjects made fewer source-based FRs compared to
passive subjects. These overall results for the effect of active navigation are
discussed in terms of the distinction between item-specific and relational
processing.
PMID- 22044788
TI - Influence of temporal overlap on time course of the Simon effect.
AB - Two experiments are reported in which we manipulated relevant and irrelevant
stimulus dimensions to assess whether an increase in temporal overlap would
influence the time course of a "standard" Simon effect (obtained when visual
stimuli are presented on the left/right of the screen and left/right responses
are performed with uncrossed hands). This procedure is new in two ways: First,
the manipulations were intended to reduce, instead of increase, the distance
between conditional and unconditional response-activation processes. Second, we
manipulated the relevant and irrelevant stimulus dimensions in a manner that did
not vary stimulus onset asynchronies, precues, or go/no go trials, or alter the
stimulus quality. Results were consistent with the hypothesis that when the two
response processes are shifted closer to each other, the Simon effect would be
sustained across time, instead of decreasing as typically found. These findings
are discussed in line with the temporal overlap hypothesis and with an automatic
activation account.
PMID- 22044789
TI - Space-time compatibility effects in the auditory modality.
AB - Previous research suggests that past and future temporal concepts are spatially
represented from left to right along a mental line. And these concepts can both
prime motor responses to left or right space and direct visual spatial attention.
The present study aimed at investigating the nature of this space-time conceptual
metaphor in different auditory tasks. In the first experiment, subjects
categorized time-related words (past or future) that were presented binaurally.
In the second experiment, subjects detected left-ear or right-ear targets
following time-related words. The similar space-time compatibility effects were
found in these two experiments. Our results demonstrate that the activation of
temporal concepts can both prime motor responses to left or right space and
influence the orientation of auditory spatial attention, suggesting that the
modality of the stimulus input is unimportant for the left-right mapping of time.
These results are explained by the "intermediate coding" account.
PMID- 22044790
TI - On coding the position of letters in words: a test of two models.
AB - Open-bigram and spatial-coding schemes provide different accounts of how letter
position is encoded by the brain during visual word recognition. Open-bigram
coding involves an explicit representation of order based on letter pairs, while
spatial coding involves a comparison function operating over representations of
individual letters. We identify a set of priming conditions (subset primes and
reversed interior primes) for which the two types of coding schemes give opposing
predictions, hence providing the opportunity for strong scientific inference.
Experimental results are consistent with the open-bigram account, and
inconsistent with the spatial-coding scheme.
PMID- 22044791
TI - Twenty-four hours of total sleep deprivation selectively impairs attentional
networks.
AB - Performance decrements after sleep loss have been extensively studied and are
usually attributed to generic attentional deficits. This claim, however, is based
on the view of attention as a unitary construct, despite evidence that it should
be considered a multidimensional cognitive ability. The aim of the present study
was to evaluate the impact of one night of sleep deprivation on the efficiency of
three attentional networks, defined by Posner and Raichle (1994) in anatomical
and functional terms, as alerting, orienting, and executive control. Thirty
participants performed the Attention Network Test at 9:00 a.m. following two
different sleep conditions: baseline (a normal night of sleep) and deprivation
(24 hrs of wakefulness). Results showed an overall slowing in reaction times and
a significant decrease in accuracy after sleep deprivation. Sleep deprivation
selectively affected the three attentional networks, given that only executive
control efficacy significantly decreased after sleep deprivation. By contrast,
phasic alerting and orienting showed no differences in the two sleep conditions.
Thus, performance deficits following sleep deprivation do not reflect global
attentional deficits.
PMID- 22044792
TI - Double cardiac silhouette on lateral chest x-ray graphy.
PMID- 22044794
TI - A prospective registry of European haemophilia B patients receiving nonacog alfa,
recombinant human factor IX, for usual use.
AB - Nonacog alfa, a recombinant factor IX (FIX) used for the treatment of haemophilia
B, was approved in Europe in 1998. In accordance with European Medicines Agency
requirements, a registry study was conducted from 2002 to 2009. A reformulated
iso-osmotic version was approved for European use in 2007. This study was
conducted to evaluate the safety of nonacog alfa in a usual care setting, and
provide clinical trial and postmarketing surveillance data support. This open
label, non-interventional, prospective observational cohort study (registry)
comprised 52 sites in nine European countries. Patients with haemophilia B
receiving nonacog alfa in either formulation for prevention or treatment were
followed on a usual care schedule. A total of 218 patients were enrolled, of whom
66 (30.3%) were <18 years of age. Haemophilia severity was evenly distributed,
with baseline FIX activity of <1%, 1-5% and >5% in 33.3%, 36.6% and 30.1% of
patients, respectively. One hundred thirty-eight patients received the original
formulation alone; 80 switched to or received only the new formulation. There was
a low incidence of events of special interest (ESIs), with less-than-expected
therapeutic effect in five patients (2.2%), inhibitor development in two (0.9%),
thrombosis in one (0.5%) and allergic events in eight (3.7%). These accounted for
the majority of the 15 serious AEs reported in six patients. Six patients
discontinued because of AEs, primarily related to hypersensitivity. Nonacog alfa
was shown to be safe for the treatment of haemophilia B, with a low incidence of
serious AEs and ESIs.
PMID- 22044795
TI - Meta-analysis: vertebroplasty for vertebral compression fracture ineffective in
improving pain and function.
PMID- 22044797
TI - Social support needs for equity in health and social care: a thematic analysis of
experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis.
AB - BACKGROUND: Needs-based resource allocation is fundamental to equitable care
provision, which can meet the often-complex, fluctuating needs of people with
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This has posed
challenges both for those providing and those seeking support providers, in
building shared understanding of the condition and of actions to address it. This
qualitative study reports on needs for equity in health and social care expressed
by adults living with CFS/ME. METHODS: The participants were 35 adults with
CFS/ME in England, purposively selected to provide variation in clinical
presentations, social backgrounds and illness experiences. Accounts of
experienced needs and needs-related encounters with health and social services
were obtained through a focus group (n = 6) and semi-structured interviews (n =
35). These were transcribed and needs related topics identified through data-led
thematic analysis. FINDINGS: Participants emphasised needs for personalised,
timely and sustained support to alleviate CFS/ME impacts and regain life control,
in three thematic areas: (1) Illness symptoms, functional limitations and illness
management; (2) practical support and social care; (3) financial support. Access
of people with CFS/ME to support from health and social services was seen to be
constrained by barriers stemming from social, cultural, organisational and
professional norms and practices, further heightened for disadvantaged groups
including some ethnic minorities. These reduced opportunities for their illness
to be explained or associated functional limitations and social disadvantages to
be addressed through social support. Participants sought more understanding of
bio-psycho-social aspects of CFS/ME, of felt needs of people with CFS/ME and of
human rights and disability rights, for providing person-centred, equitable care.
CONCLUSIONS: Changes in attitudes of health practitioners, policy makers and
general public and more flexibly organised health and social care provision are
needed to address equity issues in support needs expressed by people with CFS/ME,
to be underpinned by research-based knowledge and communication, for public and
professional education. Policy development should include shared decision-making
and coordinated action across organizations working for people with CFS/ME, human
rights and disadvantaged groups. Experiences of people with CFS/ME can usefully
inform an understanding of equity in their health and social care.
PMID- 22044796
TI - Parallel screening of FDA-approved antineoplastic drugs for identifying
sensitizers of TRAIL-induced apoptosis in cancer cells.
AB - BACKGROUND: Tumor Necrosis Factor-alpha Related Apoptosis Inducing Ligand (TRAIL)
and agonistic antibodies to death receptor 4 and 5 are promising candidates for
cancer therapy due to their ability to induce apoptosis selectively in a variety
of human cancer cells, while demonstrating little cytotoxicity in normal cells.
Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and
promising candidates in cancer therapy, many malignant cells are resistant to DR
mediated, TRAIL-induced apoptosis. In the current work, we screened a small
library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to
identify candidates that sensitized resistant prostate and pancreatic cancer
cells to TRAIL-induced apoptosis. METHODS: FDA-approved drugs were screened for
their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using
an MTT assay for cell viability. Analysis of variance was used to identify drugs
that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were
selected as leads and tested in different prostate and pancreatic cancer cell
lines, and one immortalized human pancreatic epithelial cell line. Sequential and
simultaneous dosing modalities were investigated and the annexin V/propidium
iodide assay, in concert with fluorescence microscopy, was employed to visualize
cells undergoing apoptosis. RESULTS: Fourteen drugs were identified as having
synergy with TRAIL, including those whose TRAIL sensitization activities were
previously unknown in either prostate or pancreatic cancer cells or both. Five
leads were tested in additional cancer cell lines of which, doxorubicin,
mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular,
mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led
to reduction of cancer cell viability at concentrations lower than 1 MUM. At
these low concentrations, mitoxantrone demonstrated selectivity toward malignant
cells over normal pancreatic epithelial cells. CONCLUSIONS: The identification of
a number of FDA-approved drugs as TRAIL sensitizers can expand chemotherapeutic
options for combination treatments in prostate and pancreatic cancer diseases.
PMID- 22044798
TI - Structure-activity relationship of sphingomyelin analogs with sphingomyelinase
from Bacillus cereus.
AB - The aim of this study was to examine how structural properties of different
sphingomyelin (SM) analogs affected their substrate properties with
sphingomyelinase (SMase) from Bacillus cereus. Using molecular docking and
dynamics simulations (for SMase-SM complex), we then attempted to explain the
relationship between SM structure and enzyme activity. With both micellar and
monolayer substrates, 3O-methylated SM was found not to be degraded by the SMase.
2N-methylated SM was a substrate, but was degraded at about half the rate of its
2NH-SM control. PhytoPSM was readily hydrolyzed by the enzyme. PSM lacking one
methyl in the phosphocholine head group was a good substrate, but PSM lacking two
or three methyls failed to act as substrates for SMase. Based on literature data,
and our docking and MD simulations, we conclude that the 3O-methylated PSM fails
to interact with Mg(2+) and Glu53 in the active site, thus preventing hydrolysis.
Methylation of 2NH was not crucial for binding to the active site, but appeared
to interfere with an induced fit activation of the SMase via interaction with
Asp156. An OH on carbon 4 in the long-chain base of phytoPSM appeared not to
interfere with the 3OH interacting with Mg(2+) and Glu53 in the active site, and
thus did not interfere with catalysis. Removing two or three methyls from the PSM
head group apparently increased the positive charge on the terminal N
significantly, which most likely led to ionic interactions with Glu250 and Glu155
adjacent to the active site. This likely interaction could have misaligned the SM
substrate and hindered proper catalysis.
PMID- 22044799
TI - Functional redundancy and compensation among members of gap junction protein
families?
AB - Gap junctions are intercellular conduits for small molecules made up by protein
subunits called connexins. A large number of connexin genes were found in mouse
and man, and most cell types express several connexins, lending support to the
view that redundancy and compensation among family members exist. This review
gives an overview of the current knowledge on redundancy and functional
compensation - or lack thereof. It takes into account the different properties of
connexin subunits which comprise gap junctional intercellular channels, but also
the compatibility of connexins in gap junctions. Most insight has been gained by
the investigation of mice deficient for one or more connexins and transgenic mice
with functional replacement of one connexin gene by another. Most single
deficient mice show phenotypical alterations limited to critical developmental
time points or to specific organs and tissues, while mice doubly deficient for
connexins expressed in the same cell type usually show more severe phenotypical
alterations. Replacement of a connexin by another connexin in some cases gave
rise to rescue of phenotypical alterations of connexin deficiencies, which were
restricted to specific tissues. In many tissues, connexin substitution did not
restore phenotypical alterations of connexin deficiencies, indicating that
connexins are specialized in function. In some cases, fatal consequences arose
from the replacement. The current consensus gained from such studies is that
redundancy and compensation among connexins exists at least to a limited extent.
This article is part of a Special Issue entitled: The Communicating junctions,
composition, structure and characteristics.
PMID- 22044800
TI - Trait anxiety and the dynamics of attentional control.
AB - According to recent theoretical approaches dispositional anxiety is fundamentally
linked to neural mechanisms of cognitive control (Braver et al., 2007; Eysenck et
al., 2007). The present study was conducted to further investigate this topic by
focusing on the relation between trait anxiety, conflict-processing and dynamic
adjustments in attentional allocation. Participants completed a modified version
of the face-word Stroop task while an electroencephalogram was recorded. We
analyzed behavioral and electrophysiological correlates of conflict processing
and conflict-driven modulations in target and distractor processing. Anxiety was
not related to general conflict-sensitivity but to individual differences in
conflict-driven adjustments in attentional allocation: following a high level of
stimulus-response conflict, highly anxious participants allocated more
attentional resources to the processing of predominantly task-relevant
information and withdrew attention from the processing of predominantly task
irrelevant information. Thus, trait anxiety appears to be closely related to
individual differences in dynamic adjustments of attentional control.
PMID- 22044801
TI - Mapping of positive selection sites in the HIV-1 genome in the context of RNA and
protein structural constraints.
AB - BACKGROUND: The HIV-1 genome is subject to pressures that target the virus
resulting in escape and adaptation. On the other hand, there is a requirement for
sequence conservation because of functional and structural constraints. Mapping
the sites of selective pressure and conservation on the viral genome generates a
reference for understanding the limits to viral escape, and can serve as a
template for the discovery of sites of genetic conflict with known or unknown
host proteins. RESULTS: To build a thorough evolutionary, functional and
structural map of the HIV-1 genome, complete subtype B sequences were obtained
from the Los Alamos database. We mapped sites under positive selective pressure,
amino acid conservation, protein and RNA structure, overlapping coding frames,
CD8 T cell, CD4 T cell and antibody epitopes, and sites enriched in AG and AA
dinucleotide motives. Globally, 33% of amino acid positions were found to be
variable and 12% of the genome was under positive selection. Because interrelated
constraining and diversifying forces shape the viral genome, we included the
variables from both classes of pressure in a multivariate model to predict
conservation or positive selection: structured RNA and alpha-helix domains
independently predicted conservation while CD4 T cell and antibody epitopes were
associated with positive selection. CONCLUSIONS: The global map of the viral
genome contains positive selected sites that are not in canonical CD8 T cell, CD4
T cell or antibody epitopes; thus, it identifies a class of residues that may be
targeted by other host selective pressures. Overall, RNA structure represents the
strongest determinant of HIV-1 conservation. These data can inform the combined
analysis of host and viral genetic information.
PMID- 22044802
TI - Global disparities in cancer care: the ABCD for access and the inverse care law.
PMID- 22044803
TI - Human papilloma virus: a new risk factor in a subset of head and neck cancers.
AB - Head and neck cancer is the sixth most common malignancy worldwide. Tobacco
smoking and alcohol consumption are two well known behavioral risk factors
associated with head and neck cancer. Recently, evidence is mounting that
infection with human papilloma virus, most commonly human papilloma virus-16 is
responsible for a subset of head and neck squamous cell carcinoma especially
tumors of tonsillar origin. The molecular pathway used by human papilloma virus
to trigger malignant transformation of tissue is different from that of other
well known risk factors, i.e. smoking and alcohol, associated with squamous cell
carcinoma. Apparently, these subsets of patients with human papilloma virus
positive tumor are more likely to have a better prognosis than human papilloma
virus negative tumor. Considering this fact, the human papilloma virus infection
should be determined in all oropharyngeal cancers since it can have a major
impact on the decision making process of the treatment.
PMID- 22044804
TI - Bone health in breast cancer survivors.
AB - The objective of this paper is to carry out a systemic review of the literature
investigating issues related to bone health in survivors of breast cancer. Given
the fact that only a fraction of women with breast cancer receive appropriate
assessment of their bone health, it is hoped that this review will help raise
awareness of bone health concerns in this patient population. Articles published
in the English language addressing issues related to bone health in breast cancer
were accessed using Pubmed database. Studies were searched using keywords like:
"Osteoporosis", "osteopenia", "bone health", "breast cancer", "denosumab" and
"bisphosphonates". Current evidence suggests that women who survive their breast
cancer are at high risk for significant bone loss. Recent clinical guidelines
recommend assessment of bone mineral density (BMD) in high-risk patients.
Nonpharmacologic interventions including lifestyle changes, vitamin D and calcium
supplements are extremely important. Bisphosphonates, in both oral and parenteral
formulations, are increasingly used while new agents, like denosumab, have
recently been approved. Due to the widespread use of screening mammography and
early detection programs leading to breast cancer diagnosis at a much earlier
stage and the recent introduction of more effective anticancer therapy, more
women are surviving their breast cancer, which highlights the need for
survivorship programs that address issues like bone health. Many recent
professional societies are addressing these issues and updating their
recommendations and guidelines.
PMID- 22044805
TI - Chemotherapy, neurotoxicity, and cognitive changes in breast cancer.
AB - Chemotherapy-induced cognitive changes have come under immense speculation in
recent years. This mild cognitive impairment evinced in the form of short-term
memory loss, and attention and concentration problems, finds itself unavoidably
attached to the terms 'chemobrain' or 'chemofog'. The predicament between
chemotherapy (CT) and neurotoxicity has been considerably examined and most of
its attributes have been documented through neuropsychological studies. Although
a sizeable portion of literature now covers this phenomenon, certain
methodological reservations come in the way of its full appreciation, limited
mostly by standardization issues in neuropsychological studies. The current
review discusses some of these issues, with emphasis on the underlying mechanisms
of progressing cognitive dysfunction in the breast cancer population,
accentuating a frontosubcortical involvement and the use of competent
neuropsychological batteries and structural and functional imaging techniques, to
analyze the changes associated with chemotherapy. The relevance of prospective
longitudinal studies with culture-centric norms has been emphasized, with the
need for clinical guidelines, to assess and follow the course of neurotoxicity.
Keeping track of the patient's own perceptive cognitive loss will help harmonize
the decision-making process during chemotherapy.
PMID- 22044806
TI - Clinical outcome of patients with uterine sarcomas.
AB - PURPOSE: The aim of our retrospective analysis was to study and report the
clinical outcome of patients with uterine sarcoma (US) treated at our center; and
to share our experience with literature. MATERIALS AND METHODS: We retrieved the
information regarding the patient's demography, clinico-pathological details,
treatment given, survival, and complications of all the US patients treated at
our center between the years 2000-2008. The three-year overall survival (OS) was
determined with respect to various prognostic factors like age, stage of disease,
histopathological type, adjuvant RT etc. RESULTS: A total of 50 case records were
retrieved for this retrospective analysis. Age ranged from 24 to 75 years with a
median of 50 years. Carcinosarcoma was the commonest histopathological type
(23/50 patients). FIGO stage distribution was: stage I, 27; stage II, 7; stage
III, 12; stage IV, 2; and unknown stage, two patients. Forty-eight patients
underwent surgery; 31 received postoperative radiation therapy (PORT) and 16
received chemotherapy therapy. Median follow-up period was 34 months (range 2-69
months). The three-year OS for the entire group of patients was 42%. Stage of the
disease, histopathological type, and use of PORT were found significant
prognostic factors for survival. CONCLUSION: Although limited by small sample
size and retrospective nature, ours is the only study on US being reported from
India. Our results have demonstrated FIGO stage of the disease, histopathology
and use of PORT to be the significant prognostic factor for survival. Use of
chemotherapy in future trials is warranted.
PMID- 22044808
TI - Quantitative and qualitative analysis of argyrophilic nuclear organizer regions
in follicular cyst, keratocystic odontogenic tumor and ameloblastoma.
AB - BACKGROUND: Multicystic ameloblastoma is a benign odontogenic tumor that exhibits
a more aggressive behavior than keratocystic odontogenic tumor (KCOT) and
follicular cyst. AIM: The purpose of the study was to evaluate the proliferation
index nuclear organizer regions (NORs) and their distribution among the four
odontogenic lesions with known different clinical invasive behavior. STUDY AND
DESIGN: In a descriptive-analytical cross-sectional study, 60 paraffin blocks of
odontogenic lesions were prepared for silver nitrate staining. MATERIALS AND
METHODS: For the quantitative analysis, 100 cells were counted at *100 and the
mean value was calculated. The morphometric analysis of NORs showed that they can
be distributed into normal (round to oval-shaped) and abnormal (large, bean
shaped and cluster-shaped) groups. One-way analysis of variance (ANOVA) and
multiple comparison with Tukey test were used for the statistical analysis of the
results. RESULTS: The argyrophilic NOR (AgNOR) numbers in multicystic
ameloblastoma, unicystic ameloblastoma, KCOT, and follicular cyst were 7.4 +/-
2.7, 6.1 +/- 2.56, 4.7 +/- 1.84, and 2.82 +/- 1.052, respectively. The difference
between ameloblastoma (unicystic and multicystic types) and either_KCOT, or
follicular cyst was statistically significant (P<0.001) and, (P=0.001),
respectively. In follicular cysts, normal AgNOR dots were not detected outside
the nuclei. NOR histological patterns of KCOT were large, bean shaped and rarely
cluster shaped and it was cluster-shaped in multicystic and unicystic
ameloblastoma. CONCLUSION: The current study suggests that determination of
clinical behavior of ameloblastoma in comparison with KCOT and follicular cyst in
silver nitrate staining is related to higher proliferation activity and different
NORs' distribution pattern. However, further clinical follow-up studies must be
performed to prove this.
PMID- 22044807
TI - Assessment of quality of life of cancer patients in a tertiary care hospital of
South India.
AB - BACKGROUND: Quality of Life (QOL) measures have now become a vital part of health
outcome appraisal and an effective way of capturing the personal and social
context of patients. AIM: To assess the QOL of cancer patients by using a
validated questionnaire. SETTINGS AND DESIGN: A prospective study in the medical
oncology clinic of a tertiary care hospital of South India. MATERIALS AND
METHODS: Patients receiving chemotherapy for different types of cancer were
subjected to a validated questionnaire and their responses to the factors of the
questionnaire were scored and analyzed. A Chi-square test was performed to assess
the effect of age and type of cancer on the QOL of patients. Pearson's
correlation was done to assess the factors that had greater influence on the QOL.
RESULTS: A total of 32 (15 males; 17 females) patients were included and majority
were in the age range of 61-80 years. Eleven types of cancer were identified.
About 56% of the patients were assessed to have average QOL and 28% had below
average QOL, 9% had above average, and 2 (6.25%) had significantly high QOL. The
overall mean QOL score of the study population was 122.38 +/- 13.86. Factors 1
(psychological well-being), 2 (self-adequacy), 3 (physical wellbeing), 4
(confidence in self-ability), 6 (pain), 7 (mobility), and 8 (optimism and belief)
had significant influence on the QOL, while factors 5 (external support), 9
(interpersonal relationship), and 10 (self-sufficiency and independence) did not
have a significant effect on QOL. Age (P=0.396) and type of cancer (P=0.371) did
not have a significant effect on the QOL. CONCLUSION: The study showed that 80%
of the total study population reported to have average and below average QOL,
suggesting that an increasing importance is given to the incorporation of Quality
of Life as an outcome, in addition to other clinical endpoints.
PMID- 22044809
TI - Study of the cytogenetic and non-cytogenetic factors in cervical carcinoma in the
Jammu region of J and K state.
AB - AIM: The present study was aimed to analyze the chromosomal changes and also to
work out the association of some of the non-cytogenetic factors in the confirmed
cases of cervical carcinoma. MATERIALS AND METHODS: Slides for the chromosome
study were prepared from the tumor growths of 78 patients as the diagnosed cases
of cervical carcinoma. The slides so prepared were then subjected to G-banding to
rule the involvement of different chromosomes in the progression of cervical
cancer. Non-cytogenetic factors that are considered to be the risk factors for
CaCx were also taken up during the present study to study the etiology of
cervical cancer. RESULTS: Both the numerical and the structural chromosomal
changes have been recorded in a majority of these growths. In most of the cases,
numerical chromosomal changes (95%) outnumbered the structural aberrations.
DISCUSSION: Aneuploidy was the most common numerical chromosomal aberration
recorded in the majority of the tumor growths. Structural aberrations included
translocations and deletions. Non-cytogenetic factors like multiparity, early
marriage, poor genital hygiene and rural background were highly prevalent in the
present study.
PMID- 22044810
TI - Inter and intraobserver variation in gross tumor delineation on megavoltage CT
images in patients undergoing tomotherapy-based image-guided radiotherapy for
postoperative vault recurrences.
AB - PURPOSE: This study was designed to evaluate inter and intraobserver concordance
in gross tumor volume (GTV) delineation on megavoltage CT (MVCT) images in
patients with postoperative vault recurrences. MATERIALS AND METHODS: Three
observers delineated GTV on MVCT and CECT and two observers recontoured on MVCT
images. Tumor volumes were calculated and correlated using Spearman correlation.
The standard deviation of centre of mass was averaged on per patient basis. The
ratio of common volume and encompassing volume was used to determine intra and
interobserver spatial concordance. Lack of difference in spatial concordance
ratio between MVCT and CECT images was used as an index of usability of MVCT
images. RESULTS: Thirty six datasets were available for seven patients. High
intraobserver GTV correlation was recorded for observer 1 and 2 (r = 0.93 and r =
0.98; P=0.03 and 0.0001). The average intraobserver spatial concordance ratio was
0.57 and 0.62 respectively. The mean GTV of observers 1, 2 and 3 were 31.6 (18.7
52.2); 28.2 (16.7-51.8) and 46.3 cc (29.1-90.5) respectively. Average standard
deviation of centre of mass of all observers was less than 5 mm in either
direction. Largest interobserver discordance was observed in anterior, inferior
and lateral direction. The interobserver spatial concordance of GTV on MVCT and
CECT images was 0.34 and 0.36 (P=0.24) respectively. CONCLUSION: Moderate to good
inter and intraobserver GTV correlation was observed on MVCT images, however, was
associated with low interobserver spatial concordance on both MVCT and CECT
images. Strategies to improve contouring reproducibility on MVCT and KVCT images
are desirable.
PMID- 22044811
TI - Additional rectal and sigmoid mucosal points and doses in high dose rate
intracavitary brachytherapy for carcinoma cervix: a dosimetric study.
AB - BACKGROUND: Late rectal and sigmoid toxicities seen in cervical cancer patients
are attributed to brachytherapy despite rectal doses within tolerance limits. The
purpose of this study was to identify additional dosimetric points which may
better forecast rectal complications. MATERIALS AND METHODS: Fifteen high dose
rate intracavitary brachytherapy (ICA-HDR) applications with conventional X-ray
and computed tomography (CT) based planning were studied. In addition to
International Commission on Radiation Units and Measurement (ICRU) rectal and
bladder points, proximal and distal rectal and sigmoid points were digitized on
CT scans and dose volume histograms' (DVHs') parameters were computed and
correlated. RESULTS: The mean ICRU, additional distal, proximal and sigmoid point
doses were 486 +/- 152 cGy, 527 +/- 156 cGy, 401 +/- 149 cGy and 838 +/- 254 cGy,
respectively, for a prescription of 700 cGy to point A. The mean sigmoid point
dose was significantly higher than the ICRU rectal point doses (P=0.001). The
high-dose sigmoid points were situated at a mean -8 mm (range -22.95 to 10.43 mm)
lateral, 10 mm posterior (range -15.87 to 27.82 mm) and 31 mm (range 8.08-62.91
mm) cranial to the intracavitary applicator flange of central tandem.
CONCLUSIONS: Our dosimetric study suggests that sigmoid points and 0.1 cm 3
receive significantly higher doses than rectal points during ICA-HDR in carcinoma
of the uterine cervix. No definite conclusion on reproducible spatial
distribution on orthogonal X-rays could be achieved. To document and reduce
sigmoid doses, some form of 3D image-based planning is necessary.
PMID- 22044812
TI - A comparative study to evaluate the efficacy of on board imaging with cone beam
CT using target registration in patients with lung tumors undergoing stereotactic
body radiation therapy and comparison with ExacTrac using skeletal registration
on Novalis Tx.
AB - BACKGROUND: Stereotactic body radiation therapy is an advanced technique, which
delivers ablative doses to lung lesions. Target verification is done either by
orthogonal x-rays or cone beam CT. This study was undertaken to compare these two
verification methods. AIM: To evaluate the efficacy of ExacTrac and Cone Beam
Computed Tomography (CBCT) for target repositioning while delivering Stereotactic
Body Radiation Therapy (SBRT) for lung lesions and derive the population-based
margin. MATERIALS AND METHODS: All patients who had undergone SBRT for lung
lesions from February to September 2009 were involved. Patients were immobilized
using the BodyFix double vacuum immobilization system, indexed to the computed
tomography (CT) simulator and treatment machine. Four-dimensional (3-D) scan was
done to generate internal target volume (ITV) and a free breathing CT scan for
planning was done on the BrainLab iPlan 4.1 software. During treatment, patient's
position was verified using ExacTrac and CBCT. The resulting vertical, lateral,
and longitudinal shifts were noted. The random and systematic error were
calculated and the margin recipe derived using the Van Herk formula. RESULTS:
Sixteen patients had undergone SBRT for lung tumors from February to September
2009. Data from eight patients who had undergone 34 sessions of SBRT was
analyzed. The systematic error for lateral, longitudinal, and vertical shifts for
ExacTrac and CBCT were 3.68, 4.27, 3.5 mm and 0.53, 0.38, 0.70 mm, respectively.
The random error were 1.10, 1.51, 1.96 mm and 0.32, 0.81, 0.59 mm. The lateral,
longitudinal and vertical Van Herk margin recipe for ExacTrac were 9.98, 11.72,
10.18 mm, respectively, and for CBCT was 2.17, 1.53,1.55 mm. CONCLUSIONS: The
systematic and random errors for CBCT were significantly lesser as compared to
the errors with Exactrac.
PMID- 22044813
TI - Estimation of inhomogenity correction factors for a Co-60 beam using Monte Carlo
simulation.
AB - AIM: The aim was to obtain inhomogenity correction factors (ICFs) for lung tissue
inhomogenity for a Co-60 teletherapy beam using Monte Carlo simulation and to
compare them with factors obtained from a commercially available treatment
planning system. MATERIALS AND METHODS: The Monte Carlo simulation code of EGSnrc
is used for the depth dose calculations. Two clinical like situations were
simulated-dose calculation point beyond the lung tissue volume and dose
calculation point within the lung tissue volume. The variation of ICF with lung
thicknesses and positions was studied. ICF values were obtained for the similar
situations from a commercially available treatment planning system, Theraplan
Plus. RESULTS: Percentage depth dose data obtained from Monte Carlo simulation is
well matching with the published measurement data. ICFs for lung tissue
inhomogenity calculated using the Monte Carlo code are in good agreement with
Theraplan Plus TPS values for small inhomogenity thicknesses. CONCLUSION: These
results can be used for the verification of TPS calculation or manual treatment
time calculation.
PMID- 22044814
TI - In vitro and in vivo targeted delivery of photosensitizers to the tumor cells for
enhanced photodynamic effects.
AB - BACKGROUND: Efficacy of photodynamic therapy can be enhanced by improving uptake,
localization, and sub-cellular localization of sensitizers at the sensitive
targets. MATERIALS AND METHODS: Uptake, localization, and photodynamic effects of
hematoporphyrin derivative (HpD, Photosan-3; PS-3) and disulfonated aluminum
phthalocyanine (AlPcS2) were studied either encapsulated in liposomes or
conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) in a
brain glioma cell line, BMG-1. RESULTS: Although the total uptake with
encapsulated or conjugated sensitizers was less than the free sensitizers,
photodynamic efficiency was higher due to the localization of the sensitizer at
the sensitive targets. Biodistribution of intravenously administered technetium
(99m Tc)-labeled PS-3 analyzed by gamma camera imaging showed maximum
accumulation in the liver followed by tumor. Tumor/muscle (T/N) ratio of free PS
3 was higher compared to encapsulated or conjugated PS-3 but the accumulation of
PS-3 significantly reduced in brain and cutaneous tissue following modulated
delivery. Pharmacokinetics suggested faster accumulation of encapsulated and
conjugated PS-3 in the tumor. CONCLUSION: Localization of sensitizers at
sensitive targets and reduced accumulation in normal tissues with liposome
encapsulation and antibody conjugation suggest that these two delivery systems
can potentially enhance the efficacy of photodynamic treatment.
PMID- 22044815
TI - Survivin-deltaEx3: a novel biomarker for diagnosis of papillary thyroid
carcinoma.
AB - CONTEXT: The most important problem in the case of thyroid nodules is the lack of
suitable criteria for detecting malignant thyroid tumors from other nodules in
the early stage. Variable expressions level of survivin, an inhibitory protein in
apoptotic pathway, and its splice variants in malignant carcinoma versus well
differentiated normal tissues candidate them as reliable biomarkers in cancers.
AIM: To semi-quantitative detection of survivin and its splice variant, survivin
deltaEx3, in thyroid nodules. SETTING AND DESIGN: We evaluated the expression
level of mentioned biomarkers in thyroid nodules including carcinoma. MATERIALS
AND METHODS: Samples were collected from 61 thyroid nodules including malignant,
adenoma, non-tumoral (goiter and thyroidities) as well as non-neoplastic normal
tissues. Transcriptional levels were measured using semi-quantitative reverse
transcriptase-polymerase chain reaction (RT-PCR) and the results were normalized
to beta2microglubin (beta2m) gene. STATISTICAL ANALYSIS USED: Independent sample
t-test was used to assess the significant variation of expression between
different groups. RESULT: Our data for a first time revealed that survivin
deltaEx3 is significantly up-regulated from normal to malignant thyroid carcinoma
tissues (approximately ten fold). CONCLUSION: High expression level of survivin
and survivin-deltaEx3 in malignant papillary thyroid carcinoma suggested survivin
gene expression and its splice variant, survivin-deltaEx3, can be potential new
markers in diagnosis of human papillary thyroid carcinoma.
PMID- 22044816
TI - Invasion is not an independent prognostic factor in high-grade glioma.
AB - PURPOSE: The role of invasion as a prognostic factor in high-grade gliomas (HGG)
remains controversial. An apparent increase in invasiveness following anti
angiogenic therapy makes this question clinically relevant. The goal of this
study is to assess survival differences in patients with newly diagnosed HGG who
present with diffuse invasive disease compared to those who did not, but went on
to develop diffuse invasive disease following bevacizumab therapy. MATERIALS AND
METHODS: Twenty-three patients presented as newly diagnosed diffuse invasive HGG.
All patients underwent surgical resection with radiation therapy and temozolomide
for one year. Progression-free survival (PFS) and overall survival (OS) were
compared to a control of 58 patients with focal high-grade glioma who received
similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks.
RESULTS: The patient characteristics were similar in each group. The median PFS
and OS for invasive HGG patients were 6 and 13 months and for the focal HGG
patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup
of invasive HGG that showed significant angiogenesis, the median PFS and OS were
3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse
invasive relapse. For patients with focal HGG who recurred as invasive disease,
the median PFS and OS were 9 and 21 months respectively. CONCLUSIONS: Presence of
diffuse invasive disease not accompanied by angiogenesis either prior to therapy
or subsequent to anti-angiogenic therapy does not seem to have prognostic
significance. However, invasion accompanied by angiogenesis in newly diagnosed
HGG may confer a poor prognosis.
PMID- 22044817
TI - Malignant melanoma with osteoclast-like giant cells: A report of two cases.
PMID- 22044818
TI - Adult T-cell leukemia in India: report of two cases and review of literature.
PMID- 22044819
TI - Fluoro-deoxy glucose-avid endobronchial inflammatory myofibroblastic tumor
mimicking bronchial malignancy: report of a case.
PMID- 22044820
TI - Large cell neuroendocrine carcinoma of the retromolar trigone.
PMID- 22044821
TI - Rituximab induced myocardial infarction: A fatal drug reaction.
PMID- 22044822
TI - A rare cause of acute abdomen: perforated primary sarcomatoid carcinoma of the
small intestine - report of a case, with a brief review of the literature.
PMID- 22044823
TI - Synchronous primary gall bladder carcinoma and renal transitional cell carcinoma
in the same patient: a rare case.
PMID- 22044824
TI - Solid alveolar rhabdomyosarcoma with spindle-shaped cells and epithelial
differentiation of the mediastinum in a 68-year-old man: a case report and
literature review.
PMID- 22044825
TI - Carcinoma cervix with metastasis to the orbit: a case report and review of
literature.
PMID- 22044826
TI - Adenocarcinoma lung in a painter.
PMID- 22044827
TI - Fluorodeoxyglucose positron emission tomography-computed tomography scan and
nuclear magnetic resonance findings in a case of Stewart-Treves syndrome.
PMID- 22044828
TI - A fatal case of pure giant cell carcinoma of the lung.
PMID- 22044829
TI - Oncological progression of bone plasmacytoma to POEMS syndrome.
PMID- 22044830
TI - Malignant melanotic neuroectodermal tumor of infancy arising in the mandible.
PMID- 22044831
TI - Mantle cell lymphoma presenting as Mikulicz syndrome.
PMID- 22044832
TI - Giant solitary fibrous tumor of the mesentery: a rare case.
PMID- 22044833
TI - Giant axillary swelling alongwith multiple ulcers: primary malignant adnexal
tumor-a rare distinct clinicopathologic entity.
PMID- 22044834
TI - Off-label use of chemotherapy drugs: look before you leap.
PMID- 22044835
TI - Choriocarcinoma with brain involvement.
PMID- 22044837
TI - Primary paraganglioma of thyroid presenting as solitary thyroid mass.
PMID- 22044838
TI - Second primary malignancy of breast in a patient of gastrointestinal stromal
tumor presenting as fluoro-deoxyglucose-avid breast incidentaloma in fluoro
deoxyglucose-positron emission tomography.
PMID- 22044839
TI - Hand-mirror cell morphology of T-cell lymphoproliferative disorder presenting in
pleural effusion with mediastinal widening.
PMID- 22044840
TI - Anticancer drug irinotecan inhibits homomeric 5-HT3A and heteromeric 5-HT3AB
receptor responses.
AB - It has been shown that anti-cancer drug induces secretion of serotonin (5-HT)
from small intestine which activates serotonin type 3 (5-HT(3)) receptor to cause
nausea and vomiting. In general, antagonist for 5-HT(3) receptor is used as anti
emetics during chemotherapy. However, we found that anti-cancer drug irinotecan
itself inhibits 5-HT-gated current through the homomeric 5-HT(3A) and heteromeric
5-HT(3AB) receptor in a concentration-dependent manner. The inhibitory effect of
irinotecan on 5-HT(3A) receptor was more potent than that on 5-HT(3AB) receptor.
On the other hand, SN-38, a metabolite of irinotecan, had no effect on the
responsiveness. Our findings suggest that irinotecan itself could have anti
emetic activities through inhibition of the 5-HT(3A) and 5-HT(3AB) receptor.
PMID- 22044842
TI - Factors associated with physical activity in patients with osteoarthritis of the
hip or knee: a systematic review.
AB - OBJECTIVE: To give an overview of factors related to the level of physical
activity in patients with hip or knee osteoarthritis (OA). METHODS: An extensive
systematic literature search was conducted in PubMed, CINAHL and Embase.
Inclusion criteria were: studies on patients with a diagnosis of OA of hip and/or
knee, studies describing factors related to physical activity (objective or
subjective), full length articles that were published in Dutch, German or English
language. Two reviewers independently assessed the methodological quality. A best
evidence synthesis was performed for factors which were investigated in two or
more studies. RESULTS: Eight studies were included, all with a cross-sectional
design (five high quality and three low quality studies), resulting in, at most,
limited evidence in the best-evidence synthesis. For patients with knee OA there
is limited evidence that a lower level of physical function is associated with a
lower level of physical activity. There is also limited evidence that depression
is not associated with the level of physical activity. For patients with hip OA
there is limited evidence that higher age, higher body mass index (BMI) and a low
level of physical function is associated with a low level of physical activity.
CONCLUSION: A high age (hip OA), a high BMI (hip OA) and a low level of physical
function (both hip and knee OA) are related to a low level of physical activity.
However, the level of evidence was only limited. Before new strategies and
interventions to increase physical activity in patients with OA can be developed,
high quality longitudinal studies are needed to get more insight in the causality
between factors and low levels of physical activity.
PMID- 22044841
TI - The diagnostic performance of MRI in osteoarthritis: a systematic review and meta
analysis.
AB - OBJECTIVE: Osteoarthritis (OA) is currently diagnosed using clinical and
radiographic findings. In recent years magnetic resonance imaging (MRI) use in OA
has increasingly been studied. This study was conducted to determine the
diagnostic utility of MRI in OA through a meta-analysis of published studies.
METHODS: A systematic literature search was undertaken to include studies that
used MRI to evaluate or detect OA. MRI was compared to various reference
standards: histology, arthroscopy, radiography, CT, clinical evaluation, and
direct visual inspection. Sensitivity, specificity, positive predictive value
(PPV), negative predictive value (NPV), and receiver operating characteristic
(ROC) area under the curve (AUC) were calculated. Random-effects models were used
to pool results. RESULTS: Of 20 relevant studies identified from the literature,
16 reported complete data and were included in the meta-analysis, with a total of
1220 patients (1071 with OA and 149 without). Overall sensitivity from pooling
data of all the included studies was 61% [95% confidence interval (CI) 53-68],
specificity was 82% (95% CI 77-87), PPV was 85% (95% CI 80-88), and NPV was 57%
(95% CI 43-70). The ROC showed an AUC of 0.804. There was significant
heterogeneity in the above parameters (I(2)>83%). With histology as the reference
standard, sensitivity increased to 74% and specificity decreased to 76% compared
with all reference standards combined. When arthroscopy was used as the reference
standard, sensitivity increased to 69% and specificity to 93% compared with all
reference standards combined. CONCLUSION: MRI can detect OA with an overall high
specificity and moderate sensitivity when compared with various reference
standards, thus lending more utility to ruling out OA than ruling it in. The
sensitivity of MRI is below the current clinical diagnostic standards. At this
time standard clinical algorithm for OA diagnosis, aided by radiographs appears
to be the most effective method for diagnosing OA.
PMID- 22044843
TI - Effect of body mass index-z score on adverse levels of cardiovascular disease
risk factors.
AB - BACKGROUND: Cardiovascular disease (CVD) risk factors are associated with body
mass index z-score (BMISD) and/or insulin resistance (IR). However, the
correlation between adverse levels of these risk factors and BMISD, and the
effect of IR on these associations are not fully understood in children. The aim
of this study was to evaluate the association between adverse levels of CVD risk
factors and BMISD, and the effect of IR on these associations in schoolchildren.
METHODS: Conventional CVD risk factors, C-reactive protein (CRP), uric acid (UA)
and adiponectin were determined in 757 boys and 494 girls aged between 7 and 12
years. IR was assessed by the homeostasis model approximation index. RESULTS:
BMISD were linearly associated with relative risks having adverse levels of all
factors, except for glucose and low-density lipoprotein cholesterol (LDL-C) in
boys, and except for glucose, LDL-C and adiponectin in girls (P < 0.01-0.001).
These associations were weakened after adjustment for IR, but still significant
in cases of UA and CRP in boys and UA, high-density lipoprotein cholesterol and
CRP in girls (P < 0.01-0.001). CONCLUSION: The relative risk of having adverse
levels of most CVD risk factors in school children increased across the entire
range of BMISD. IR contributed to most of these relative risks, but BMISD itself
also contributed to these relative risks. To prevent future development of CVD,
it might be important for schoolchildren to maintain BMISD within normal range.
However, in cases of hyper LDL-cholesterolemia, we should consider causes other
than BMISD.
PMID- 22044844
TI - Antiviral mode of action of bovine dialyzable leukocyte extract against human
immunodeficiency virus type 1 infection.
AB - BACKGROUND: Bovine dialyzable leukocyte extract (bDLE) is derived from immune
leukocytes obtained from bovine spleen. DLE has demonstrated to reduce
transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the
nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
signaling pathway. Therefore, we decided to clarify the mode of antiviral action
of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays.
RESULTS: The cytotoxicity, HIV-1 inhibition activity, residual infectivity of
bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for
fusogenic cells and the duration of cell protection even after the removal of
bDLE were all assessed in order to discover more about the mode of the antiviral
action.HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic
for HeLa-CD4-LTR-beta-gal cells. Pretreatment of HIV-1 with bDLE did not decrease
the infectivity of these viral particles. Cell-based fusion assays helped to
determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane
fusion and this cell-based fusion was inhibited only when CD4 cells were treated
with bDLE. Infection was inhibited in 80% compared with the positive (without
EDL) at all viral life cycle stages in the time of addition experiments when bDLE
was added at different time points. Finally, a cell-protection assay against HIV
1 infection by bDLE was performed after treating host cells with bDLE for 30
minutes and then removing them from treatment. From 0 to 7 hours after the bDLE
was completely removed from the extracellular compartment, HIV-1 was then added
to the host cells. The bDLE was found to protect the cells from HIV-1 infection,
an effect that was retained for several hours. CONCLUSIONS: bDLE acted as an
antiviral compound and prevented host cell infection by HIV-1 at all viral life
cycle stages. These cell protection effects lingered for hours after the bDLE was
removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only
on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect
on target cells after it was removed from the extracellular compartment,
protecting the cells from infection for hours.bDLE, which has no reported side
effects or toxicity in clinical trials, should therefore be further studied to
determine its potential use as a therapeutic agent in HIV-1 infection therapy, in
combination with known antiretrovirals.
PMID- 22044846
TI - Robust modeling based on optimized EEG bands for functional brain state
inference.
AB - The need to infer brain states in a data driven approach is crucial for BCI
applications as well as for neuroscience research. In this work we present a
novel classification framework based on Regularized Linear Regression classifier
constructed from time-frequency decomposition of an EEG (electro-encephalography)
signal. The regression is then used to derive a model of frequency distributions
that identifies brain states. The process of classifier construction,
preprocessing and selection of optimal regularization parameter by means of cross
validation is presented and discussed. The framework and the feature selection
technique are demonstrated on EEG data recorded from 10 healthy subjects while
requested to open and close their eyes every 30 s. This paradigm is well known in
inducing Alpha power modulations that differ from low power (during eyes opened)
to high (during eyes closed). The classifier was trained to infer eyes opened or
eyes closed states and achieved higher than 90% classification accuracy.
Furthermore, our findings reveal interesting patterns of relations between
experimental conditions, EEG frequencies, regularization parameters and
classifier choice. This viable tool enables identification of the most
contributing frequency bands to any given brain state and their optimal
combination in inferring this state. These features allow for much greater detail
than the standard Fourier Transform power analysis, making it an essential method
for both BCI proposes and neuroimaging research.
PMID- 22044845
TI - The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor
activity of trastuzumab against HER2/neu-expressing breast cancer.
AB - BACKGROUND: HER2/neu is an oncogene that facilitates neoplastic transformation
due to its ability to transduce growth signals in a ligand-independent manner, is
over-expressed in 20-30% of human breast cancers correlating with aggressive
disease and has been successfully targeted with trastuzumab (Herceptin(r)).
Because trastuzumab alone achieves only a 15-30% response rate, it is now
commonly combined with conventional chemotherapeutic drugs. While the combination
of trastuzumab plus chemotherapy has greatly improved response rates and
increased survival, these conventional chemotherapy drugs are frequently
associated with gastrointestinal and cardiac toxicity, bone marrow and immune
suppression. These drawbacks necessitate the development of new, less toxic drugs
that can be combined with trastuzumab. Recently, we reported that orally
administered alpha-tocopheryloxyacetic acid (alpha-TEA), a novel ether derivative
of alpha-tocopherol, dramatically suppressed primary tumor growth and reduced the
incidence of lung metastases both in a transplanted and a spontaneous mouse model
of breast cancer without discernable toxicity. METHODS: In this study we examined
the effect of alpha-TEA plus HER2/neu-specific antibody treatment on HER2/neu
expressing breast cancer cells in vitro and in a HER2/neu positive human
xenograft tumor model in vivo. RESULTS: We show in vitro that alpha-TEA plus anti
HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor
cells and human breast cancer cells and that the anti-tumor effect of alpha-TEA
is independent of HER2/neu status. More importantly, in a human breast cancer
xenograft model, the combination of alpha-TEA plus trastuzumab resulted in faster
tumor regression and more tumor-free animals than trastuzumab alone. CONCLUSION:
Due to the cancer cell selectivity of alpha-TEA, and because alpha-TEA kills both
HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential
to be effective and less toxic than existing chemotherapeutic drugs when used in
combination with HER2/neu antibody.
PMID- 22044847
TI - Signals from intraventricular depth electrodes can control a brain-computer
interface.
AB - A brain-computer interface (BCI) is a device that enables severely disabled
people to communicate and interact with their environments using their brain
waves. Most research investigating BCI in humans have used scalp-recorded
electroencephalography (EEG). We have recently demonstrated that signals from
intracranial electrocorticography (ECoG) and stereotactic depth electrodes (SDE)
in the hippocampus can be used to control a BCI P300 Speller paradigm. We report
a case in which stereotactic depth electrodes positioned in the ventricle were
able to obtain viable signals for a BCI. Our results demonstrate that event
related potentials from intraventricular electrodes can be used to reliably
control the P300 Speller BCI paradigm.
PMID- 22044848
TI - Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach.
AB - Iron can cause oxidative stress and DNA damage, and heme iron can catalyze
endogenous formation of N-nitroso compounds, which are potent carcinogens.
Dietary iron promotes esophageal cancer incidence in animal studies and has been
identified as a growth factor for Helicobacter pylori, an established risk factor
for stomach cancer. We conducted a population-based case-control study of
adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in
Nebraska. Heme iron and total iron intake were estimated from a food frequency
questionnaire and databases of heme and total iron. We used logistic regression
to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for
known risk factors. Esophageal cancer was positively associated with higher
intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and
total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P
trend=0.050). Risk of stomach cancer was elevated among those with higher intakes
of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron
from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all
dietary sources was not significantly associated with risk of either cancer. Our
results suggest that high intakes of heme and iron from meat may be important
dietary risk factors for esophageal and stomach cancer and may partly explain
associations with red meat.
PMID- 22044850
TI - Antioxidant agents in the prevention of hepatocellular carcinoma.
PMID- 22044849
TI - A longitudinal study of the metabolic syndrome and risk of colorectal cancer in
postmenopausal women.
AB - The metabolic syndrome is associated with increased risk of diabetes and coronary
heart disease. Although higher BMI and other related factors have been frequently
associated with colorectal cancer, whether the metabolic syndrome is associated
with the risk of colorectal cancer is unclear. We therefore assessed the
association of the metabolic syndrome with the risk of colorectal cancer in a
subsample of participants of the Women's Health Initiative who had repeated
measurements of the components of the syndrome at baseline and during follow-up.
Women with diabetes at baseline enrollment were excluded. Cox proportional
hazards models were used to estimate hazard ratios (HRs) and 95% confidence
intervals (95% CI) at baseline and in time-dependent analyses. Among 4862
eligible women, 81 incident cases of colorectal cancer were identified over a
median follow-up of 12 years. Presence of the metabolic syndrome at baseline was
associated with increased risk of colorectal cancer (HR 2.15, 95% CI 1.30-3.53)
and colon cancer (HR 2.28, 95% CI 1.31-3.98). These associations were largely
explained by positive associations of serum glucose and systolic blood pressure
with both outcomes. Time-dependent covariate analyses supported the baseline
findings. Our results suggest that the positive association of the metabolic
syndrome with risk of colorectal cancer is largely accounted for by serum glucose
levels and systolic blood pressure. The biological mechanism underlying these
associations remains to be clarified.
PMID- 22044851
TI - Risk of cancer of unknown primary among immigrants to Sweden.
AB - Incidence of cancer of unknown primary (CUP) varies globally, and environmental
factors are suspected to be related to its development. Immigrant studies offer
insights into disease etiology, but no studies have been published on CUP. We
investigated CUP risk in immigrants to Sweden to search for etiological clues.
The nationwide Swedish Family Cancer Database was used to calculate standardized
incidence ratios for CUP in the first-generation immigrants compared with native
Swedes from 1958 to 2008. A total of 2340 patients with CUP were identified among
immigrants during a follow-up of 23 million person-years compared with 30 507
patients with CUP identified in native Swedes who were followed for 260 million
person-years, showing an overall standardized incidence ratio of 0.88 (95%
confidence interval: 0.85-0.93). The median age at immigration was 28 years for
men and 27 for women. Significantly lower CUP risks, ranging from 0.18 to 0.89,
were mainly observed among Finnish, German, and Asian immigrants. The decreased
risks tended to be lower for women compared with men. Danes of both sexes had an
increased risk. The increased or decreased CUP risks observed in this novel study
suggested that early life environmental risk factors or genetic factors influence
the development of CUP. The risk patterns were modified by sex. The observed
differences may give clues about incidence rates in countries of origin for which
incidence data are lacking.
PMID- 22044852
TI - A combination of resveratrol and melatonin exerts chemopreventive effects in N
methyl-N-nitrosourea-induced rat mammary carcinogenesis.
AB - The neurohormone melatonin is primarily involved in the regulation of circadian
rhythms, but also acts as an antioxidant and anticarcinogenic agent, especially
in breast cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a widely
known polyphenolic agent from red wine, which has been shown to exert
antioxidant, anti-inflammatory and anticarcinogenic effects. The objective of
this study was therefore to investigate the effects of melatonin in combination
with resveratrol in a rat model of experimental mammary carcinogenesis. Female
Sprague-Dawley rats aged 31 days were used in the experiment. Mammary
carcinogenesis was induced by N-methyl-N-nitrosourea (NMU), which was
administered in two intraperitoneal doses (50 mg/kg of body weight).
Chemoprevention with resveratrol and melatonin started 2 weeks before the first
dose of NMU and lasted until the end of the experiment. The basic parameters
evaluated were: tumour incidence, latency period, tumour frequency per group and
tumour volume. In addition, oestrogen receptors ERalpha and ERbeta, melatonin
receptor MT1, proliferating cell nuclear antigen and vascular endothelial growth
factor were determined by immunohistochemical staining. The combination of
resveratrol and melatonin reduced tumour incidence by approximately 17% and
significantly decreased the quantity of invasive and in-situ carcinomas. Food
intake declined in the second and seventh weeks after the administration of
carcinogen. Resveratrol in combination with melatonin returned food intake to the
level of intact controls. Resveratrol in combination with melatonin has some
protective effects on NMU-induced rodent breast cancer. Further studies are
necessary to confirm these effects of this promising combination.
PMID- 22044853
TI - Human breast tumor slices as an alternative approach to cell lines to
individualize research for each patient.
AB - There are several breast cancer experimental models including cell lines, which
are commonly used due to ease of handling and storage. However, the continued
propagation of cell lines and distribution among laboratories results in genetic
drift and distancing from the in-vivo model. Primary organ culture of breast
cancer slices may produce biological responses with high standard deviation for
different samples, reflecting the heterogeneity of different tumors. Thus, the
organ culture model system offers a new perspective to the results obtained in
the cell lines and offers an alternative for studies that seek to individualize
treatment for each patient, an increasingly prominent concern in current cancer
therapy.
PMID- 22044854
TI - Comparative effectiveness of efavirenz, protease inhibitors, and raltegravir
based regimens as first-line treatment for HIV-infected adults: a mixed treatment
comparison.
AB - OBJECTIVE: Compare the efficacy of 2 NRTIs combined with raltegravir (RAL),
efavirenz (EFV), or protease inhibitors (PI) in the management of antiretroviral
naive HIV adult patients. METHODS: By means of a systematic literature view, 7
randomized controlled trials were identified: 2 RAL vs EFV trials; 1 ritonavir
boosted lopinavir (LPV/RTV) vs EFV trial; 1 ritonavir-boosted atazanavir
(ATV/RTV) vs LPV/RTV trial; 1 ritonavir-boosted darunavir (DRV/RTV) vs LPV/RTV
trial; 1 ritonavir-boosted fosamprenavir (FPV/RTV) vs LPV/RTV trial; and 1
FPV/RTV vs ATV/RTV trial. Endpoints concerned virological suppression and
immunologic efficacy. Trials were analyzed with Bayesian mixed treatment
comparison meta-analysis. RESULTS: For up to 24 weeks of treatment, a PI-based
regimen resulted in a lower proportion of patients with virological response than
an EFV-based regimen, whereas RAL seems more efficacious than EFV up to at least
12 weeks. After 48 weeks, the odds ratio (OR) of virological suppression with RAL
relative to EFV was 1.34 (95% credible interval [CrI], 0.87-2.07). ORs for PIs
relative to EFV varied from 0.68 (0.41-1.07) with LPV/RTV to 0.99 (0.52-1.84)
with DRV/RTV. RAL demonstrated a greater improvement in CD4+ T cell counts than
EFV at 48 weeks. The PI regimens showed all similar improvements relative to EFV.
CONCLUSION: Based on available RCTs, the fastest virological suppression is
expected with RAL followed by EFV and PIs. Over time, RAL appears to be at least
as good as PI and EFV regimens. CD4+ cell recovery seems the greatest with
LPV/RTV, DRV/RTV, and RAL. Given the limited number of RCTs, additional studies
are recommended.
PMID- 22044855
TI - Incidence rate of and factors associated with loss to follow-up in a longitudinal
cohort of antiretroviral-treated HIV-infected persons: an AIDS Clinical Trials
Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) analysis.
AB - PURPOSE: Examine incidence and factors associated with loss to follow-up (LTFU)
in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials
(ALLRT) cohort. METHOD: ALLRT is a prospective cohort of HIV-infected persons
randomized to antiretroviral (ARV) regimens/strategies in ACTG trials and
followed long-term after the trial ends. Person-years were calculated from ALLRT
entry until loss to follow-up (LTFU; defined using off-study reasons or >= 3
consecutive missed visits), death/ severe debilitation/site closures, or June
2009 (censored). Poisson regression was used to examine LTFU factors separately
among participants who were ARV naive or ARV experienced at trial entry. RESULTS:
Among 4,630 participants (22,524 person-years), 1,140 were lost to follow-up, 237
died, 29 were severely debilitated, and 443 were at sites that closed. The LTFU
incidence was 5.5 and 4.2 per 100 person-years among previously ARV-naive and ARV
experienced participants, respectively. In both groups, age <= 50, site location,
being off ARVs, and viral load >= 400 copies/mL were associated with a higher
risk of LTFU. Among ARV-naive participants, male sex, education <16 years,
intravenous drug use, and cigarette smoking were also associated with LTFU.
CONCLUSION: Knowledge of differential LTFU can help researchers identify
participants at risk of LTFU in longitudinal HIV cohorts and design retention
strategies, thereby limiting study bias. The identified factors should be
included in inverse probability of weighting models to account for LTFU.
PMID- 22044857
TI - Assessment of vascular function in HIV-infected patients.
AB - PURPOSE: The vascular function in HIV-infected persons under HAART and non-HIV
infected persons was investigated. METHOD: 18 HIV-positive patients and 23 HIV
negative subjects (14 younger group and 9 older group) were evaluated for
microvascular vasodilatation during postocclusive reactive hyperemia (PORH) and
during prolonged local thermal hyperemia; overall microvascular flux increase
induced by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP)
and large artery stiffness (SI(DVP)). RESULTS: Cutaneous vascular conductance
(CVC) responses to ACh were lower in HIV patients compared to both HIV-negative
groups (mean [SEM]) (HIV positive: 878.2 [99.5]; older HIV negative: 1129.3
[231.6]; younger HIV negative: 1366.5 [172.6] % baseline). Regarding SNP
iontophoresis, HIV-positive and older HIV-negative groups showed lower CVC
responses than younger HIV-negative group (HIV positive: 1043.0 [164.6]; older
HIV-negative: 980.8 [108.3]; younger HIV-negative: 1757.3 [245.1] % baseline).
Vasodilatation induced by thermal hyperemia (HIV positive: 1.63 [0.11]; older HIV
negative: 1.48 [0.08]; younger HIV negative: 1.85 [0.27] perfusion units/mm Hg)
and PORH (HIV positive: 0.374 [0.025]; older HIV negative: 0.326 [0.025]; younger
HIV negative: 0.326 [0.037] PU/mm Hg) were similar between all groups. SIDVP was
greater in HIV and older healthy groups than younger healthy group (HIV positive:
9.17 [0.42]; older HIV negative: 8.19 [0.43]; younger HIV negative: 6.42 [0.22]
m/s). CONCLUSION: HIV-infected patients under HAART exhibited slight but
nonsignificant lower microvascular reactivity to pharmacological stimuli and
increased arterial stiffness compared to age-matched HIV-negative subjects.
Comparison of both HIV-positive and older HIV-negative groups with younger HIV
negative subjects suggests that age plays a major role in microvascular
reactivity regardless the HIV-infection.
PMID- 22044856
TI - A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for
protease inhibitor-based regimens in antiretroviral-experienced HIV-infected
individuals: week 48 results of the A5146 study.
AB - BACKGROUND: We devised an open-label, randomized trial to evaluate whether
therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose
escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI
trough concentration and drug resistance, could improve virologic outcome in PI
experienced patients with treatment failure. Secondary analyses through 48 weeks
are presented. METHODS: Eligible HIV-infected subjects with a screening viral
load of >= 1000 copies/mL initiated a new PI-based regimen at entry and had NIQ
performed at week 2. Subjects with an NIQ <=1 were randomized at week 4 to a
standard-of-care (SOC) arm or TDM arm featuring PI dose escalation. RESULTS: One
hundred and eighty-three subjects were randomized. There was no significant
treatment difference in change from randomization to week 48 in HIV-1 RNA [ P =
.13, median (25th, 75th percentile log10 copies/mL change): -0.03 (-0.74, 0.62)
with TDM and 0.11 (-2.3, 0.82) with SOC]. In subgroup analysis, patients with >=
0.69 active PIs benefited from TDM compared to those with <0.69 active PIs ( P =
.05). CONCLUSIONS: While the TDM strategy of PI dose escalation did not improve
virologic response at week 48 overall, in subgroup analysis, TDM favorably
impacted virologic outcome in subjects taking PI-based regimens with moderate
antiviral activity.
PMID- 22044858
TI - Body mass index and CD4+ T-lymphocyte recovery in HIV-infected men with viral
suppression on antiretroviral therapy.
AB - PURPOSE: To better characterize the relationship between body mass index (BMI)
and CD4+ T-lymphocyte recovery in HIV disease. METHODS: We analyzed the
association between baseline BMI and CD4+ T-lymphocyte increases, as well as the
association between BMI and immune activation (CD38 and HLA-DR co-expression on
CD4+ and CD8+ T-lymphocytes), in male HIV-infected patients who achieved viral
suppression on antiretroviral therapy (ART). RESULTS: Baseline BMI predicted
change in CD4+ T-lymphocyte count at weeks 96 ( P = .03, n = 461) and 144 ( P =
.005, n = 357) but not at week 48 ( P = .38, n = 558). Relative to men with a
normal BMI, overweight and obese men had increases at week 144 that were 35 and
113 cells/ mm3 higher, respectively, while underweight men had CD4+ T-lymphocyte
increases that were 94 cells/mm3 lower. No significant correlations between
baseline BMI and cellular immune activation were seen. CONCLUSIONS: BMI predicts
CD4+ T-lymphocyte gains in men started on ART.
PMID- 22044859
TI - 96-week results of a pilot study of abacavir/lamivudine and raltegravir in
antiretroviral-naive HIV-1-infected patients: the SHIELD trial.
PMID- 22044862
TI - A prospective comparison of cardiac magnetic resonance imaging and radionuclide
ventriculography in the assessment of cardiac function in patients treated with
anthracycline-based chemotherapy.
AB - PURPOSE: To compare cardiac MRI and radionuclide ventriculography (RVG) in
cardiac monitoring during anthracycline (doxorubicin)-based chemotherapy.
MATERIALS AND METHODS: We studied 10 previously untreated adult non-Hodgkin
lymphoma patients. Left ventricular ejection fraction (LVEF) was assessed by MRI
and RVG simultaneously. In addition, left ventricular (LV) and left atrial size
were determined by MRI. Both MRI and RVG measurements were determined at baseline
and then repeated after eight cycles of CHOP chemotherapy (cumulative doxorubicin
dose of 400 mg/m2). Power calculations were made on the basis of reproducibility
measurements. RESULTS: Clinical heart failure was not observed in any patient
during the study. MRI detected a statistically significant increase in LV end
diastolic volume (128 +/- 39 vs. 151 +/- 46 ml, P<0.05) and LV mass (119 +/- 32
vs. 146 +/- 49 g, P<0.05) after doxorubicin therapy but no change in LVEF (46 +/-
8 vs. 47 +/- 11%, P=NS) or left atrial area. A significant LVEF reduction
compared with baseline was observed by RVG (61 +/- 10 vs. 50 +/- 6%, P<0.01). On
average, MRI resulted in 7 +/- 10% lower LVEF values compared with RVG.
CONCLUSION: RVG seems to be a valuable and repeatable tool in detecting early,
subclinical deterioration in cardiac function and is the method of choice in the
follow-up of LV function during anthracycline-based chemotherapy. Whether LV
volumetric and mass changes found in MRI could predict later significant
permanent cardiac damage should be evaluated in larger studies with long-term
follow-up.
PMID- 22044863
TI - Fully automatic synthesis of [18F]FES for reporter gene hERL expression imaging.
AB - We have developed a fully automatic method for the synthesis of 16alpha
[18F]fluoroestradiol ([F]FES) using a TRACERlab FXFN module. Following
[18F]fluorination, the intermediate was hydrolyzed with a mixture of 2 N HCl in
acetonitrile (CH3CN) and then neutralized with sodium bicarbonate (NaHCO3). After
HPLC purification, the decay-corrected radiochemical yield of [18F]FES was 50 +/-
2.35% (n=4), which was stable up to 96.1 +/- 0.3% (n=4) at 8 h. This new fully
automated synthesis method provided high and reproducible yields and the produced
[F]FES could be used to monitor in-vivo human estrogen receptor alpha ligand
binding domain gene expression using PET images.
PMID- 22044864
TI - Evaluation of PET volume segmentation methods: comparisons with expert manual
delineations.
AB - INTRODUCTION: [18F]-Fluorodeoxyglucose PET has become an essential technique in
oncology. Accurate segmentation is important for treatment planning. With the
increasing number of available methods, it will be useful to establish a reliable
evaluation tool. METHOD: Five methods for [F]-fluorodeoxyglucose PET image
segmentation (MIP-based, Fuzzy C-means, Daisne, Nestle and the 42% threshold
based approach) were evaluated on non-Hodgkin's lymphoma lesions by comparing
them with manual delineations performed by a panel of experts. The results were
analyzed using different similarity measures. Intraoperator and interoperator
variabilities were also studied. RESULTS: The maximum of intensity projection
based method provided results closest to the manual delineations set [binary
Jaccard index mean (SD) 0.45 (0.15)]. The fuzzy C-means algorithm yielded
slightly less satisfactory results. The application of a 42% threshold-based
approach yielded results furthest from the manual delineations [binary Jaccard
index mean (SD) 0.38 (0.16)]; the Daisne and the Nestle methods yielded
intermediate results. Important intraoperator and interoperator variabilities
were demonstrated. CONCLUSION: A simple assessment framework based on comparisons
with manual delineations was proposed. The use of a set of manual delineations
performed by five different experts as the reference seemed to be suitable to
take the intraoperator and the interoperator variabilities into account. The
online distribution of the data set generated in this study will make it possible
to evaluate any new segmentation method.
PMID- 22044865
TI - Ultrasound-guided sentinel node procedure for nonpalpable breast carcinoma.
AB - PURPOSE: Peritumoral and periareolar tracer injection techniques lead to
different lymphatic drainage in sentinel lymph node biopsy procedures. In a
prospective study, the visualization and identification rates of the ultrasound
(US)-guided tracer injection technique for palpable and nonpalpable breast tumors
were evaluated. METHODS: In 1262 consecutive patients with cT1-2N0 breast cancer,
sentinel lymph node biopsy was performed following peritumoral tracer injection.
In the case of nonpalpable breast lesions, Tc-99m nanocolloid injections were
given using a 7.5 MHz US probe. In the case of ultrasonographically nonvisible
microcalcifications, the US-guided injection technique was wire guided. RESULTS:
In 331 patients with nonpalpable breast lesions (26.2%), the lymphoscintigraphic
visualization and surgical retrieval rates of axillary sentinel lymph nodes
(SLNs) were 98.5 and 99.4%, respectively. For internal mammary (IM) SLNs, these
rates were 21.1 and 17.8%, respectively. These rates were similar in patients
with palpable and nonpalpable tumors. Axillary metastases were detected in 38.7%
of the patients with palpable tumors versus 16.5% of those with nonpalpable
tumors (P<0.001), whereas IM metastases were found in 4.8 and 3.0% of patients,
respectively (P=0.165). CONCLUSION: In nonpalpable breast lesions, the US-guided
injection technique is an accurate technique for SLN identification and
retrieval. The substantial rates of IM metastases in both palpable and
nonpalpable lesions favor a peritumoral tracer injection technique.
PMID- 22044866
TI - Cortical metabolites as biomarkers in the R6/2 model of Huntington's disease.
AB - To improve the ability to move from preclinical trials in mouse models of
Huntington's disease (HD) to clinical trials in humans, biomarkers are needed
that can track similar aspects of disease progression across species. Brain
metabolites, detectable by magnetic resonance spectroscopy (MRS), have been
suggested as potential biomarkers in HD. In this study, the R6/2 transgenic mouse
model of HD was used to investigate the relative sensitivity of the metabolite
profiling and the brain volumetry to anticipate the disease progression. Magnetic
resonance imaging (MRI) and (1)H MRS data were acquired at 9.4 T from the R6/2
mice and wild-type littermates at 4, 8, 12, and 15 weeks. Brain shrinkage was
detectable in striatum, cortex, thalamus, and hypothalamus by 12 weeks.
Metabolite changes in cortex paralleled and sometimes preceded those in striatum.
The entire set of metabolite changes was compressed into principal components
(PCs) using Partial Least Squares-Discriminant Analysis (PLS-DA) to increase the
sensitivity for monitoring disease progression. In comparing the efficacy of
volume and metabolite measurements, the cortical PC1 emerged as the most
sensitive single biomarker, distinguishing R6/2 mice from littermates at all time
points. Thus, neurochemical changes precede volume shrinkage and become potential
biomarkers for HD mouse models.
PMID- 22044867
TI - The roles of cerebral blood flow, capillary transit time heterogeneity, and
oxygen tension in brain oxygenation and metabolism.
AB - Normal brain function depends critically on moment-to-moment regulation of oxygen
supply by the bloodstream to meet changing metabolic needs. Neurovascular
coupling, a range of mechanisms that converge on arterioles to adjust local
cerebral blood flow (CBF), represents our current framework for understanding
this regulation. We modeled the combined effects of CBF and capillary transit
time heterogeneity (CTTH) on the maximum oxygen extraction fraction (OEF(max))
and metabolic rate of oxygen that can biophysically be supported, for a given
tissue oxygen tension. Red blood cell velocity recordings in rat brain support
close hemodynamic-metabolic coupling by means of CBF and CTTH across a range of
physiological conditions. The CTTH reduction improves tissue oxygenation by
counteracting inherent reductions in OEF(max) as CBF increases, and seemingly
secures sufficient oxygenation during episodes of hyperemia resulting from
cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF,
both lower oxygen tension and CTTH may secure tissue oxygenation. Our model
predicts that disturbed capillary flows may cause a condition of malignant CTTH,
in which states of higher CBF display lower oxygen availability. We propose that
conditions with altered capillary morphology, such as amyloid, diabetic or
hypertensive microangiopathy, and ischemia-reperfusion, may disturb CTTH and
thereby flow-metabolism coupling and cerebral oxygen metabolism.
PMID- 22044868
TI - Meteorin is a chemokinetic factor in neuroblast migration and promotes stroke
induced striatal neurogenesis.
AB - Ischemic stroke affecting the adult brain causes increased progenitor
proliferation in the subventricular zone (SVZ) and generation of neuroblasts,
which migrate into the damaged striatum and differentiate to mature neurons.
Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in
neural progenitor cells and immature neurons during development, suggesting that
it may be involved in neurogenesis. Here, we show that METRN promotes migration
of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult
rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced
apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral
artery occlusion upregulates the expression of endogenous METRN in cells with
neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged
brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and
increases the number of immature and mature neurons in the ischemic striatum. Our
findings identify METRN as a new factor promoting neurogenesis both in vitro and
in vivo by multiple mechanisms. Further work will be needed to translate METRN's
actions on endogenous neurogenesis into improved recovery after stroke.
PMID- 22044869
TI - Neurointensive care biophysiological monitoring.
AB - Monitoring various physiological parameters and their derangements provides a
valuable tool for management of severely brain injured patients. The various
parameters and their monitoring tools include but are not all inclusive are
cerebral blood flow and oxygen monitoring, jugular bulb oximetry, intracerebral
microdialysis and continuous electroencephalography. It needs to be seen how
these devices are applied to improve patient outcomes.
PMID- 22044870
TI - High rates of depressive symptomatology among injecting drug users in Saskatoon,
Canada.
PMID- 22044871
TI - An overview of animal prion diseases.
AB - Prion diseases are transmissible neurodegenerative conditions affecting human and
a wide range of animal species. The pathogenesis of prion diseases is associated
with the accumulation of aggregates of misfolded conformers of host-encoded
cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and
goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible
mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform
encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy
of primates. Although some cases of sporadic atypical scrapie and BSE have also
been reported, animal prion diseases have basically occurred via the acquisition
of infection from contaminated feed or via the exposure to contaminated
environment. Scrapie and chronic wasting disease are naturally sustaining
epidemics. The transmission of BSE to human has caused more than 200 cases of
variant Cruetzfeldt-Jacob disease and has raised serious public health concerns.
The present review discusses the epidemiology, clinical neuropathology,
transmissibility and genetics of animal prion diseases.
PMID- 22044872
TI - Maternal exercise decreases maternal deprivation induced anxiety of pups and
correlates to increased prefrontal cortex BDNF and VEGF.
AB - Maternal deprivation (MD) may cause neuropsychiatric disorders such as anxiety
disorder by negatively affecting the cognitive functions and behavior in pups.
The aim of this study is to investigate whether maternal exercise during
pregnancy has beneficial effects on anxiety that increases with MD, and on the
levels of VEGF and BDNF which have anxiolytic effects on the prefrontal cortex,
the anxiety-related region of the brain. The anxiety level in the deprivation
group was greater than the control group and found more in male than female pups.
The prefrontal cortex VEGF and BDNF levels were decreased in the deprivation
group compared to control group while serum corticosterone levels were increased
in the deprivation group. Anxiety and serum corticosterone levels were decreased
in maternally exercised female and male pups, while the prefrontal cortex VEGF
and BDNF levels were increased, compared to sedentary mother's pups. These
results indicate that maternal exercise may attenuate the negative effect of
stresses such as maternal deprivation that can be encountered early in life.
PMID- 22044873
TI - Association of biomarkers and depressive symptoms in schizophrenia.
AB - Emergence of depressive symptoms in schizophrenia results in a deteriorating
course and poor prognosis. Schizophrenia and depressive disorder are both
associated with low levels of brain-derived neurotrophic factor (BDNF) and with a
longstanding low grade inflammatory state. The objective of this study is to
analyze the relationship between these serum biomarkers and depressive and
psychotic symptoms in schizophrenic patients. Thirty-nine individuals diagnosed
with schizophrenia or schizoaffective disorder by Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV), assessed by Structured Clinical Interview
for DSM-IV (SCID), were included. Interviews were conducted with The Positive and
Negative Syndrome Scale (PANSS) and The Calgary Depression Scale for
Schizophrenia (CDSS). Blood samples were collected for determination of BDNF, IL
1beta, IL-6, IL-8, IL-10, IL-12 and TNF-alpha measurements. Positive correlations
between BDNF and CDSS and between IL-1beta and severity in PANSS scores were
found. BDNF levels were not correlated with any cytokine or with PANSS scores.
The results of this study suggest that depressive and psychotic symptoms may be
associated with different profiles of biomarkers in the association between
schizophrenia and depression.
PMID- 22044874
TI - The characterization of gene expression during mouse neural stem cell
differentiation in vitro.
AB - Neural stem cells (NSCs) are tissue-specific, multipotent stem cells that can
differentiate into three cell lineages in the central nervous system: neurons,
astrocytes and oligodendrocytes. The therapeutic potential of NSCs has fueled
attempts to characterize the expression of genes that regulate their fate. In
this study, NSCs from embryonic day 15 (E15) mouse embryos were differentiated
for 1 (DF-1) or 2 (DF-2) days, and the gene expression patterns in the NSCs and
in the DF-1 and DF-2 cells were measured by microarray and real-time RT-PCR.
Among the analyzed genes, 1898 genes were up-regulated in the DF-1 and DF-2 cells
relative to the NSCs, whereas 1642 genes were down-regulated. The up-regulated
genes included Gfap, Smad6, Fst, Tgfb2 and Cdkn2. The down-regulated genes
included Ccnb1, Ccnd1 and Ccnd2. We identified gene networks that were associated
with BMP and TGF-beta2 signaling pathways using Ingenuity Pathway Analysis. Our
results suggest that the differentiation of E15 NSCs into astrocytes is based on
a combinatorial network of various signaling pathways, including cell cycle, BMP
and TGF-beta2 signaling.
PMID- 22044875
TI - Association between 1425G/A SNP in PRKCH and ischemic stroke among Chinese and
Japanese populations: a meta-analysis including 3686 cases and 4589 controls.
AB - AIMS: Meta-analysis was performed to investigate the association between 1425G/A
SNP in PRKCH (the gene encoding for protein kinase C eta) and ischemic stroke
among Chinese and Japanese populations. METHODS: The databases of MEDLINE,
PubMed, Chinese Biomedical Database, China National Knowledge Infrastructure, and
WANFANG DATA until September 2011 were searched for published case-control
studies on 1425G/A SNP in PRKCH and ischemic stroke. Strict selection criteria
and exclusion criteria were determined, and pooled odds ratio (OR) and the 95%
confidence interval (CI) were calculated using a fixed or random effects model to
determine the strength of the genetic association. The publication bias was
further evaluated by calculating the fail-safe number in the included studies.
RESULTS: Five studies, comprising 3686 cases and 4589 controls, passed all the
criteria and therefore were included in the meta-analysis. Test for heterogeneity
showed that P values (P=0.76, 0.24, respectively) in the two meta-analyses were
both greater than 0.05, therefore the fixed effects model was performed.
Statistically significant association between 1425G/A SNP in PRKCH and ischemic
stroke was identified (OR=1.34; 95% CI, 1.22-1.47), and the association was even
stronger between 1425G/A SNP in PRKCH and lacunar infarction (OR=1.44; 95% CI,
1.28-1.63). The fail-safe number (N(fs 0.05)) for 1425G/A SNP in PRKCH with
ischemic stroke and lacunar infarction was 59 and 44, respectively, which were
greater than the number of studies included in the analyses. CONCLUSIONS: SNP
1425G/A in PRKCH was associated with ischemic stroke, particularly lacunar
infarction, in Chinese and Japanese populations. More studies of different
subtypes of stroke need to be done to confirm the results in other Asian
populations.
PMID- 22044876
TI - Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve
fibres in rat diabetic skin.
AB - In this study we have determined the amount of Nerve Growth Factor (NGF) and the
innervation density of the glabrous hindpaw skin of diabetic rats (n=4) and
controls (n=3). The proportion of intra-epidermal nerve fibres (IENF) expressing
the high affinity NGF receptor (trkA) and calcitonin gene-related peptide (CGRP)
were also determined. Four weeks after induction of diabetes by intraperitoneal
streptozotocin injection skin was analyzed for: (i) NGF content using ELISA and
(ii) the innervation density of peptidergic afferents that also expressed trkA
using immunocytochemistry. NGF levels were approximately three-fold higher in
diabetic skin compared to controls (diabetic: 134.7+/-24.0 (SD) pgml(-1),
control: 42.7+/-21.5pgml(-1), p=0.002). As expected there was a significant
reduction in IENF density in diabetic skin (2.7+/-1.3 fibresmm(-1)) compared to
controls (6.9+/-1.5 fibresmm(-1); p=0.01). In diabetic rats there was no
significant difference in the proportion of trkA-labelled IENF (diabetic 74+/
21%; control 83+/-15%, p=0.6), but significantly more trkA-positive IENF were
also labelled by CGRP antibodies in diabetic skin compared to controls (diabetic
89+/-22%; control 38+/-2%, p=0.03). These data suggest that in diabetes the
upregulation of cutaneous NGF may 'over-troph' the surviving axons, increasing
CGRP labelling, which may be important in the aetiology of painful diabetic
neuropathy.
PMID- 22044877
TI - Protective effects of lycopene against amyloid beta-induced neurotoxicity in
cultured rat cortical neurons.
AB - The neurotoxicity of amyloid beta (Abeta) has been implicated as a critical cause
in the pathogenesis of Alzheimer's disease (AD). Among antioxidant phytochemicals
derived from fruit and vegetables, lycopene has recently received considerable
attention for its potent protective properties already demonstrated in several
models of oxidative damage. The present study aims to investigate whether
lycopene could provide protective effects against Abeta-induced neurotoxicity in
primary cultured rat cortical neurons. The cultured cortical neurons were
pretreated with different dose of lycopene for 4h, followed by the challenge with
25 MUM Abeta(25-35) for 24h. The results showed that pretreatment with lycopene
efficiently attenuated Abeta(25-35)-induced neurotoxicity, as evidenced by the
improved cell viability and the decreased apoptotic rate. In addition, lycopene
inhibited the reactive oxygen species generation and mitochondrial membrane
potential depolarization caused by Abeta(25-35). Lycopene also restored the
levels of proapoptotic Bax, antiapoptotic Bcl-2, and inhibited caspase-3
activation. These beneficial effects may contribute to the protection against
Abeta-induced neurotoxicity. Together, our results suggest that the natural
antioxidant lycopene has potential for neuroprotection and therefore, may be a
promising candidate for AD treatment.
PMID- 22044878
TI - Dual inhibitors of P-glycoprotein and tumor cell growth: (re)discovering
thioxanthones.
AB - For many pathologies, there is a crescent effort to design multiple ligands that
interact with a wide variety of targets. 1-Aminated thioxanthone derivatives were
synthesized and assayed for their in vitro dual activity as antitumor agents and
P-glycoprotein (P-gp) inhibitors. The approach was based on molecular
hybridization of a thioxanthone scaffold, present in known antitumor drugs, and
an amine, described as an important pharmacophoric feature for P-gp inhibition. A
rational approach using homology modeling and docking was used, to select the
molecules to be synthesized by conventional or microwave-assisted Ullmann C-N
cross-coupling reaction. The obtained aminated thioxanthones were highly
effective at inhibiting P-gp and/or causing growth inhibition in a chronic
myelogenous leukemia cell line, K562. Six of the aminated thioxanthones had
GI(50) values in the K562 cell line below 10 MUM and 1-{[2
(diethylamino)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one (37) had a GI(50)
concentration (1.90 MUM) 6-fold lower than doxorubicin (11.89 MUM) in the K562Dox
cell line. The best P-gp inhibitor found was 1-[2-(1H-benzimidazol-2
yl)ethanamine]-4-propoxy-9H-thioxanthen-9-one (45), which caused an accumulation
rate of rhodamine-123 similar to that caused by verapamil in the K562Dox
resistant cell line, and a decrease in ATP consumption by P-gp. At a
concentration of 10 MUM, compound 45 caused a decrease of 12.5-fold in the GI(50)
value of doxorubicin in the K562Dox cell line, being 2-fold more potent than
verapamil. From the overall results, the aminated thioxanthones represent a new
class of P-gp inhibitors with improved efficacy in sensitizing a resistant P-gp
overexpressing cell line (K562Dox) to doxorubicin.
PMID- 22044879
TI - Single-unit-cell thick Mn3O4 nanosheets.
AB - Single-unit-cell thick Mn(3)O(4) sheets were synthesized in an aqueous solution
at room temperature. These nanosheets have a 500 nm), drive fast visual processes, which are largely blind to chromatic
signals from more narrowly-tuned photoreceptors with peak sensitivities in the
blue and UV regions of the spectrum. In addition, electrophysiological properties
of the photoreceptor membrane may result in differences in response dynamics of
photoreceptors of similar spectral class between species, and different spectral
classes within a species. We used intracellular electrophysiological techniques
to investigate response dynamics of the three spectral classes of photoreceptor
underlying trichromatic colour vision in the bumblebee, Bombus impatiens, and we
compare these with previously published data from a related species, Bombus
terrestris. In both species, we found significantly faster responses in green,
compared with blue- or UV-sensitive photoreceptors, although all 3 photoreceptor
types are slower in B. impatiens than in B. terrestris. Integration times for
light-adapted B. impatiens photoreceptors (estimated from impulse response half
width) were 11.3 +/- 1.6 ms for green photoreceptors compared with 18.6 +/- 4.4
ms and 15.6 +/- 4.4 for blue and UV, respectively. We also measured photoreceptor
input resistance in dark- and light-adapted conditions. All photoreceptors showed
a decrease in input resistance during light adaptation, but this decrease was
considerably larger (declining to about 22% of the dark value) in green
photoreceptors, compared to blue and UV (41% and 49%, respectively). Our results
suggest that the conductances associated with light adaptation are largest in
green photoreceptors, contributing to their greater temporal processing speed. We
suggest that the faster temporal processing of green photoreceptors is related to
their role in driving fast achromatic visual processes.
PMID- 22046252
TI - The network of global corporate control.
AB - The structure of the control network of transnational corporations affects global
market competition and financial stability. So far, only small national samples
were studied and there was no appropriate methodology to assess control globally.
We present the first investigation of the architecture of the international
ownership network, along with the computation of the control held by each global
player. We find that transnational corporations form a giant bow-tie structure
and that a large portion of control flows to a small tightly-knit core of
financial institutions. This core can be seen as an economic "super-entity" that
raises new important issues both for researchers and policy makers.
PMID- 22046253
TI - Chromatin immunoprecipitation (ChIP): revisiting the efficacy of sample
preparation, sonication, quantification of sheared DNA, and analysis via PCR.
AB - The "quantitative" ChIP, a tool commonly used to study protein-DNA interactions
in cells and tissue, is a difficult assay often plagued with technical error. We
present, herein, the process required to merge multiple protocols into a quick,
reliable and easy method and an approach to accurately quantify ChIP DNA prior to
performing PCR. We demonstrate that high intensity sonication for at least 30 min
is required for full cellular disruption and maximum DNA recovery because ChIP
lysis buffers fail to lyse formaldehyde-fixed cells. In addition, extracting ChIP
DNA with chelex-100 yields samples that are too dilute for evaluation of shearing
efficiency or quantification via nanospectrophotometry. However, DNA extracted
from the Mock-ChIP supernatant via the phenol-chloroform-isoamyl alcohol (PCIA)
method can be used to evaluate DNA shearing efficiency and used as the standard
in a fluorescence-based microplate assay. This enabled accurate quantification of
DNA in chelex-extracted ChIP samples and normalization to total DNA concentration
prior to performing real-time PCR (rtPCR). Thus, a quick ChIP assay that can be
completed in nine bench hours over two days has been validated along with a
rapid, accurate and repeatable way to quantify ChIP DNA. The resulting rtPCR data
more accurately depicts treatment effects on protein-DNA interactions of
interest.
PMID- 22046254
TI - Growth of Acinetobacter baumannii in pellicle enhanced the expression of
potential virulence factors.
AB - BACKGROUND: Interestingly, Acinetobacter baumannii presents an enhanced capacity
to form biofilms (also named pellicles) at the air-liquid interface as compared
to the other Acinetobacter species. This characteristic questions the
contribution of this phenotype to an increased risk of clinical infections by
this pathogen. METHODOLOGY/PRINCIPAL FINDINGS: By a proteomic approach using 2-D
gel electrophoresis-LC-MS/MS mass spectrometry, we compared the membrane protein
patterns of A. baumannii 77, a pellicle-forming clinical isolate, grown in
planktonic and in sessile modes. We identified 52 proteins with a differential
expression, including 32 up-regulated and 20 down-regulated in the pellicle
state. Several proteins, differentially expressed during pellicle development,
were of particular interest. We determined the over-expression of four
siderophore iron uptake systems including the acinetobactin and enterobactin
receptors and confirmed that the development of this type of biofilm is promoted
by ferric ions. Two over-expressed proteins, CarO and an OprD-homologue, putative
carbapenem-resistance associated porins, would be involved in the transport of
specific compounds, like ornithine, a biosynthesis precursor of a siderophore
from the hydroxamate family. We evidenced the overexpression of a lipase and a
transporter of LCFA that may be involved in the recycling of lipids inside the
pellicle matrix. Finally, we demonstrated both by proteomic and by AFM studies
that this particular type of biofilm required multiple pili systems to maintain
this cohesive structure at the air-liquid interface; two of these systems have
never been described in A. baumannii. CONCLUSIONS/SIGNIFICANCE: Our study
demonstrated that several proteins, overexpressed at a late state of pellicle
development, could be potentially involved in virulence processes. Therefore,
regarding the number of potential virulence factors that are over-expressed in
this growth mode, the pellicle-forming clinical isolates should be kept under
survey.
PMID- 22046255
TI - Cost-effectiveness of pharmacotherapy to reduce obesity.
AB - AIMS: Obesity causes a high disease burden in Australia and across the world. We
aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy
in Australia, and to assess its potential to reduce the disease burden due to
excess body weight. METHODS: We constructed a multi-state life-table based Markov
model in Excel in which body weight influences the incidence of stroke, ischemic
heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis,
post-menopausal breast cancer, colon cancer, endometrial cancer and kidney
cancer. We use data on effectiveness identified from PubMed searches, on
mortality from Australian Bureau of Statistics, on disease costs from the
Australian Institute of Health and Welfare, and on drug costs from the Department
of Health and Ageing. We evaluate 1-year pharmacological interventions with
sibutramine and orlistat targeting obese Australian adults free of obesity
related disease. We use a lifetime horizon for costs and health outcomes and a
health sector perspective for costs. Incremental Cost-Effectiveness Ratios
(ICERs) below A$50 000 per Disability Adjusted Life Year (DALY) averted are
considered good value for money. RESULTS: The ICERs are A$130 000/DALY (95%
uncertainty interval [UI] 93 000-180 000) for sibutramine and A$230 000/DALY (170
000-340 000) for orlistat. The interventions reduce the body weight-related
disease burden at the population level by 0.2% and 0.1%, respectively. Modest
weight loss during the interventions, rapid post-intervention weight regain and
low adherence limit the health benefits. CONCLUSIONS: Treatment with sibutramine
or orlistat is not cost-effective from an Australian health sector perspective
and has a negligible impact on the total body weight-related disease burden.
PMID- 22046256
TI - VDA, a method of choosing a better algorithm with fewer validations.
AB - The multitude of bioinformatics algorithms designed for performing a particular
computational task presents end-users with the problem of selecting the most
appropriate computational tool for analyzing their biological data. The choice of
the best available method is often based on expensive experimental validation of
the results. We propose an approach to design validation sets for method
comparison and performance assessment that are effective in terms of cost and
discrimination power.Validation Discriminant Analysis (VDA) is a method for
designing a minimal validation dataset to allow reliable comparisons between the
performances of different algorithms. Implementation of our VDA approach achieves
this reduction by selecting predictions that maximize the minimum Hamming
distance between algorithmic predictions in the validation set. We show that VDA
can be used to correctly rank algorithms according to their performances. These
results are further supported by simulations and by realistic algorithmic
comparisons in silico.VDA is a novel, cost-efficient method for minimizing the
number of validation experiments necessary for reliable performance estimation
and fair comparison between algorithms.Our VDA software is available at
http://sourceforge.net/projects/klugerlab/files/VDA/
PMID- 22046257
TI - Treatment of rat spinal cord injury with the neurotrophic factor albumin-oleic
acid: translational application for paralysis, spasticity and pain.
AB - Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often
characterized by the debilitating symptoms of paralysis, spasticity and pain,
which require treatment with novel pleiotropic pharmacological agents. Previous
in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role
together as an endogenous neurotrophic factor. Although Alb can promote basic
recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on
a known translational measure of SCI associated with symptoms of spasticity and
change in nociception has not been studied. Following T9 spinal contusion injury
in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles),
iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA
(0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of
noxious reflex activity, and with a new test of descending modulation of spinal
activity below the SCI up to one month after injury. Albumin, OA and Alb-OA
treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover
Alb-OA synergistically promoted early recovery of locomotor activity to 50 +/-
10% of control and promoted de novo phasic descending inhibition of TA noxious
reflex activity to 47 +/- 5% following non-invasive electrical conditioning
stimulation applied above the iSCI. Spinal L4-L5 immunohistochemistry
demonstrated a unique increase in serotonin fibre innervation up to 4.2 +/- 1.1
and 2.3 +/- 0.3 fold within the dorsal and ventral horn respectively with Alb-OA
treatment when compared to uninjured tissue, in addition to a reduction in NR1
NMDA receptor phosphorylation and microglia reactivity. Early recovery of
voluntary motor function accompanied with tonic and de novo phasic descending
inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment,
mediated via known endogenous spinal mechanisms of action, suggests a clinical
application of this novel neurotrophic factor for the treatment of paralysis,
spasticity and pain.
PMID- 22046258
TI - Genetic associations in the vitamin D receptor and colorectal cancer in African
Americans and Caucasians.
AB - Low vitamin D levels are associated with an increased incidence of colorectal
cancer (CRC) and higher mortality from the disease. In the US, African Americans
(AAs) have the highest CRC incidence and mortality and the lowest levels of
vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR)
gene have been previously associated with CRC, but few studies have included AAs.
We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina
as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and
Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for
association adjusting for West African ancestry, age, gender, and multiple
testing. Untyped markers were imputed using MACH1.0. We analyzed associations by
gender and anatomic location in the whole study group as well as by vitamin D
intake in the North Carolina AA group. In the joint analysis, none of the SNPs
tested was significantly associated with CRC. For four previously tested
restriction fragment length polymorphisms, only one (referred to as ApaI), tagged
by the SNP rs79628898, had a nominally significant p-value in AAs; none of these
polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs,
for whom we had vitamin D intake data, we found a significant association between
an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene
environment interaction in AAs. In summary, using a systematic tagSNP approach,
we have not found evidence for significant associations between VDR and CRC in
AAs or Caucasians.
PMID- 22046259
TI - Comprehensive network analysis of anther-expressed genes in rice by the
combination of 33 laser microdissection and 143 spatiotemporal microarrays.
AB - Co-expression networks systematically constructed from large-scale transcriptome
data reflect the interactions and functions of genes with similar expression
patterns and are a powerful tool for the comprehensive understanding of
biological events and mining of novel genes. In Arabidopsis (a model dicot
plant), high-resolution co-expression networks have been constructed from very
large microarray datasets and these are publicly available as online information
resources. However, the available transcriptome data of rice (a model monocot
plant) have been limited so far, making it difficult for rice researchers to
achieve reliable co-expression analysis. In this study, we performed co
expression network analysis by using combined 44 K agilent microarray datasets of
rice, which consisted of 33 laser microdissection (LM)-microarray datasets of
anthers, and 143 spatiotemporal transcriptome datasets deposited in RicexPro. The
entire data of the rice co-expression network, which was generated from the 176
microarray datasets by the Pearson correlation coefficient (PCC) method with the
mutual rank (MR)-based cut-off, contained 24,258 genes and 60,441 genes pairs.
Using these datasets, we constructed high-resolution co-expression subnetworks of
two specific biological events in the anther, "meiosis" and "pollen wall
synthesis". The meiosis network contained many known or putative meiotic genes,
including genes related to meiosis initiation and recombination. In the pollen
wall synthesis network, several candidate genes involved in the sporopollenin
biosynthesis pathway were efficiently identified. Hence, these two subnetworks
are important demonstrations of the efficiency of co-expression network analysis
in rice. Our co-expression analysis included the separated transcriptomes of
pollen and tapetum cells in the anther, which are able to provide precise
information on transcriptional regulation during male gametophyte development in
rice. The co-expression network data presented here is a useful resource for rice
researchers to elucidate important and complex biological events.
PMID- 22046260
TI - Altered expression of insulin receptor isoforms in breast cancer.
AB - PURPOSE: Insulin-like growth factor (IGF) signaling through human insulin
receptor isoform A (IR-A) contributes to tumorigenesis and intrinsic resistance
to anti-IGF1R therapy. In the present study, we (a) developed quantitative TaqMan
real time-PCR-based assays (qRT-PCR) to measure human insulin receptor isoforms
with high specificity, (b) evaluated isoform expression levels in molecularly
defined breast cancer subtypes, and (c) identified the IR-A:IR-B mRNA ratio as a
potential biomarker guiding patient stratification for anti-IGF therapies.
EXPERIMENTAL DESIGN: mRNA expression levels of IR-A and IR-B were measured in 42
primary breast cancers and 19 matched adjacent normal tissues with TaqMan qRT-PCR
assays. The results were further confirmed in 165 breast cancers. The tumor
samples were profiled using whole genome microarrays and subsequently subtyped
using the PAM50 breast cancer gene signature. The relationship between the IR
A:IR-B ratio and cancer subtype, as well as markers of proliferation were
characterized. RESULTS: The mRNA expression levels of IR-A in the breast tumors
were similar to those observed in the adjacent normal tissues, while the mRNA
levels of IR-B were significantly decreased in tumors. The IR-A:IR-B ratio was
significantly higher in luminal B breast cancer than in luminal A. Strong
concordance between the IR-A:IR-B ratio and the composite Oncotype DX
proliferation score was observed for stratifying the latter two breast cancer
subtypes. CONCLUSIONS: The reduction in IR-B expression is the key to the altered
IR-A:IR-B ratio observed in breast cancer. The IR-A:IR-B ratio may have biomarker
utility in guiding a patient stratification strategy for an anti-IGF therapeutic.
PMID- 22046261
TI - Mastermind mutations generate a unique constellation of midline cells within the
Drosophila CNS.
AB - BACKGROUND: The Notch pathway functions repeatedly during the development of the
central nervous system in metazoan organisms to control cell fate and regulate
cell proliferation and asymmetric cell divisions. Within the Drosophila midline
cell lineage, which bisects the two symmetrical halves of the central nervous
system, Notch is required for initial cell specification and subsequent
differentiation of many midline lineages. METHODOLOGY/PRINCIPAL FINDINGS: Here,
we provide the first description of the role of the Notch co-factor, mastermind,
in the central nervous system midline of Drosophila. Overall, zygotic mastermind
mutations cause an increase in midline cell number and decrease in midline cell
diversity. Compared to mutations in other components of the Notch signaling
pathway, such as Notch itself and Delta, zygotic mutations in mastermind cause
the production of a unique constellation of midline cell types. The major
difference is that midline glia form normally in zygotic mastermind mutants, but
not in Notch and Delta mutants. Moreover, during late embryogenesis, extra
anterior midline glia survive in zygotic mastermind mutants compared to wild type
embryos. CONCLUSIONS/SIGNIFICANCE: This is an example of a mutation in a
signaling pathway cofactor producing a distinct central nervous system phenotype
compared to mutations in major components of the pathway.
PMID- 22046262
TI - dTip60 HAT activity controls synaptic bouton expansion at the Drosophila
neuromuscular junction.
AB - BACKGROUND: Histone acetylation of chromatin plays a key role in promoting the
dynamic transcriptional responses in neurons that influence the neuroplasticity
linked to cognitive ability, yet the specific histone acetyltransferases (HATs)
that create such epigenetic marks remain to be elucidated. METHODS AND FINDINGS:
Here we use the Drosophila neuromuscular junction (NMJ) as a well-characterized
synapse model to identify HATs that control synaptic remodeling and structure. We
show that the HAT dTip60 is concentrated both pre and post-synaptically within
the NMJ. Presynaptic targeted reduction of dTip60 HAT activity causes a
significant increase in synaptic bouton number that specifically affects type Is
boutons. The excess boutons show a suppression of the active zone synaptic
function marker bruchpilot, suggesting defects in neurotransmission function.
Analysis of microtubule organization within these excess boutons using
immunohistochemical staining to the microtubule associated protein futsch reveals
a significant increase in the rearrangement of microtubule loop architecture that
is required for bouton division. Moreover, alpha-tubulin acetylation levels of
microtubules specifically extending into the terminal synaptic boutons are
reduced in response to dTip60 HAT reduction. CONCLUSIONS: Our results are the
first to demonstrate a causative role for the HAT dTip60 in the control of
synaptic plasticity that is achieved, at least in part, via regulation of the
synaptic microtubule cytoskeleton. These findings have implications for dTip60
HAT dependant epigenetic mechanisms underlying cognitive function.
PMID- 22046263
TI - Ectodermal influx and cell hypertrophy provide early growth for all murine
mammary rudiments, and are differentially regulated among them by Gli3.
AB - Mammary gland development starts in utero with one or several pairs of mammary
rudiments (MRs) budding from the surface ectodermal component of the mammalian
embryonic skin. Mice develop five pairs, numbered MR1 to MR5 from pectoral to
inguinal position. We have previously shown that Gli3(Xt-J/Xt-J) mutant embryos,
which lack the transcription factor Gli3, do not form MR3 and MR5. We show here
that two days after the MRs emerge, Gli3(Xt-J/Xt-J) MR1 is 20% smaller, and
Gli3(Xt-J/Xt-J) MR2 and MR4 are 50% smaller than their wild type (wt)
counterparts. Moreover, while wt MRs sink into the underlying dermis, Gli3(Xt
J/Xt-J) MR4 and MR2 protrude outwardly, to different extents. To understand why
each of these five pairs of functionally identical organs has its own, distinct
response to the absence of Gli3, we determined which cellular mechanisms regulate
growth of the individual MRs, and whether and how Gli3 regulates these
mechanisms. We found a 5.5 to 10.7-fold lower cell proliferation rate in wt MRs
compared to their adjacent surface ectoderm, indicating that MRs do not emerge or
grow via locally enhanced cell proliferation. Cell-tracing experiments showed
that surface ectodermal cells are recruited toward the positions where MRs
emerge, and contribute to MR growth during at least two days. During the second
day of MR development, peripheral cells within the MRs undergo hypertrophy, which
also contributes to MR growth. Limited apoptotic cell death counterbalances MR
growth. The relative contribution of each of these processes varies among the
five MRs. Furthermore, each of these processes is impaired in the absence of
Gli3, but to different extents in each MR. This differential involvement of Gli3
explains the variation in phenotype among Gli3(Xt-J/Xt-J) MRs, and may help to
understand the variation in numbers and positions of mammary glands among
mammals.
PMID- 22046264
TI - Elucidation of the ATP7B N-domain Mg2+-ATP coordination site and its allosteric
regulation.
AB - The diagnostic of orphan genetic disease is often a puzzling task as less
attention is paid to the elucidation of the pathophysiology of these rare
disorders at the molecular level. We present here a multidisciplinary approach
using molecular modeling tools and surface plasmonic resonance to study the
function of the ATP7B protein, which is impaired in the Wilson disease.
Experimentally validated in silico models allow the elucidation in the Nucleotide
binding domain (N-domain) of the Mg(2+)-ATP coordination site and answer to the
controversial role of the Mg(2+) ion in the nucleotide binding process. The
analysis of protein motions revealed a substantial effect on a long flexible loop
branched to the N-domain protein core. We demonstrated the capacity of the loop
to disrupt the interaction between Mg(2+)-ATP complex and the N-domain and
propose a role for this loop in the allosteric regulation of the nucleotide
binding process.
PMID- 22046265
TI - Oscillatory dynamics of cell cycle proteins in single yeast cells analyzed by
imaging cytometry.
AB - Progression through the cell division cycle is orchestrated by a complex network
of interacting genes and proteins. Some of these proteins are known to fluctuate
periodically during the cell cycle, but a systematic study of the fluctuations of
a broad sample of cell-cycle proteins has not been made until now. Using time
lapse fluorescence microscopy, we profiled 16 strains of budding yeast, each
containing GFP fused to a single gene involved in cell cycle regulation. The
dynamics of protein abundance and localization were characterized by extracting
the amplitude, period, and other indicators from a series of images. Oscillations
of protein abundance could clearly be identified for Cdc15, Clb2, Cln1, Cln2,
Mcm1, Net1, Sic1, and Whi5. The period of oscillation of the fluorescently tagged
proteins is generally in good agreement with the inter-bud time. The very strong
oscillations of Net1 and Mcm1 expression are remarkable since little is known
about the temporal expression of these genes. By collecting data from large
samples of single cells, we quantified some aspects of cell-to-cell variability
due presumably to intrinsic and extrinsic noise affecting the cell cycle.
PMID- 22046266
TI - High prevalence of primary multidrug resistant tuberculosis in persons with no
known risk factors.
AB - INTRODUCTION: In high multidrug resistant (MDR) tuberculosis (TB) prevalence
areas, drug susceptibility testing (DST) at diagnosis is recommended for patients
with risk factors for MDR. However, this approach might miss a substantial
proportion of MDR-TB in the general population. We studied primary MDR in
patients considered to be at low risk of MDR-TB in Lima, Peru. METHODS: We
enrolled new sputum smear-positive TB patients who did not report any MDR-TB risk
factor: known exposure to a TB patient whose treatment failed or who died or who
was known to have MDR-TB; immunosuppressive co-morbidities, ex prison inmates;
prison and health care workers; and alcohol or drug abuse. A structured
questionnaire was applied to all enrolled participants to confirm the absence of
these factors and thus minimize underreporting. Sputum from all participants was
cultured on Lowenstein-Jensen media and DST for first line drugs was performed
using the 7H10 agar method. RESULTS: Of 875 participants with complete data,
23.2% (203) had risk factors for MDR-TB elicited after enrolment. Among the group
with no reported risk factors who had a positive culture, we found a 6.3% (95%CI
4.4-8.3) (37/584) rate of MDR-TB. In this group no epidemiological
characteristics were associated with MDR-TB. Thus, in this group, multidrug
resistance occurred in patients with no identifiable risk factors. CONCLUSIONS:
We found a high rate of primary MDR-TB in a general population with no
identifiable risk factors for MDR-TB. This suggests that in a high endemic area
targeting patients for MDR-TB based on the presence of risk factors is an
insufficient intervention.
PMID- 22046267
TI - A new methodology to associate SNPs with human diseases according to their
pathway related context.
AB - Genome-wide association studies (GWAS) with hundreds of zthousands of single
nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic
basis of human complex diseases. Despite many successes of GWAS, it is well
recognized that new analytical approaches have to be integrated to achieve their
full potential. Starting with a list of SNPs, found to be associated with disease
in GWAS, here we propose a novel methodology to devise functionally important
KEGG pathways through the identification of genes within these pathways, where
these genes are obtained from SNP analysis. Our methodology is based on
functionalization of important SNPs to identify effected genes and disease
related pathways. We have tested our methodology on WTCCC Rheumatoid Arthritis
(RA) dataset and identified: i) previously known RA related KEGG pathways (e.g.,
Toll-like receptor signaling, Jak-STAT signaling, Antigen processing, Leukocyte
transendothelial migration and MAPK signaling pathways); ii) additional KEGG
pathways (e.g., Pathways in cancer, Neurotrophin signaling, Chemokine signaling
pathways) as associated with RA. Furthermore, these newly found pathways included
genes which are targets of RA-specific drugs. Even though GWAS analysis
identifies 14 out of 83 of those drug target genes; newly found functionally
important KEGG pathways led to the discovery of 25 out of 83 genes, known to be
used as drug targets for the treatment of RA. Among the previously known
pathways, we identified additional genes associated with RA (e.g. Antigen
processing and presentation, Tight junction). Importantly, within these pathways,
the associations between some of these additionally found genes, such as HLA-C,
HLA-G, PRKCQ, PRKCZ, TAP1, TAP2 and RA were verified by either OMIM database or
by literature retrieved from the NCBI PubMed module. With the whole-genome
sequencing on the horizon, we show that the full potential of GWAS can be
achieved by integrating pathway and network-oriented analysis and prior knowledge
from functional properties of a SNP.
PMID- 22046268
TI - A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas
aeruginosa biofilm formation and virulence on Caenorhabditis elegans.
AB - In Pseudomonas aeruginosa, the expression of a number of virulence factors, as
well as biofilm formation, are controlled by quorum sensing (QS). N
Acylhomoserine lactones (AHLs) are an important class of signaling molecules
involved in bacterial QS and in many pathogenic bacteria infection and host
colonization are AHL-dependent. The AHL signaling molecules are subject to
inactivation mainly by hydrolases (Enzyme Commission class number EC 3) (i.e. N
acyl-homoserine lactonases and N-acyl-homoserine-lactone acylases). Only little
is known on quorum quenching mechanisms of oxidoreductases (EC 1). Here we report
on the identification and structural characterization of the first NADP-dependent
short-chain dehydrogenase/reductase (SDR) involved in inactivation of N-(3-oxo
dodecanoyl)-L-homoserine lactone (3-oxo-C(12)-HSL) and derived from a metagenome
library. The corresponding gene was isolated from a soil metagenome and
designated bpiB09. Heterologous expression and crystallographic studies
established BpiB09 as an NADP-dependent reductase. Although AHLs are probably not
the native substrate of this metagenome-derived enzyme, its expression in P.
aeruginosa PAO1 resulted in significantly reduced pyocyanin production, decreased
motility, poor biofilm formation and absent paralysis of Caenorhabditis elegans.
Furthermore, a genome-wide transcriptome study suggested that the level of lasI
and rhlI transcription together with 36 well known QS regulated genes was
significantly (>=10-fold) affected in P. aeruginosa strains expressing the bpiB09
gene in pBBR1MCS-5. Thus AHL oxidoreductases could be considered as potent tools
for the development of quorum quenching strategies.
PMID- 22046269
TI - Cholesterol influences voltage-gated calcium channels and BK-type potassium
channels in auditory hair cells.
AB - The influence of membrane cholesterol content on a variety of ion channel
conductances in numerous cell models has been shown, but studies exploring its
role in auditory hair cell physiology are scarce. Recent evidence shows that
cholesterol depletion affects outer hair cell electromotility and the voltage
gated potassium currents underlying tall hair cell development, but the effects
of cholesterol on the major ionic currents governing auditory hair cell
excitability are unknown. We investigated the effects of a cholesterol-depleting
agent (methyl beta cyclodextrin, MbetaCD) on ion channels necessary for the early
stages of sound processing. Large-conductance BK-type potassium channels underlie
temporal processing and open in a voltage- and calcium-dependent manner. Voltage
gated calcium channels (VGCCs) are responsible for calcium-dependent exocytosis
and synaptic transmission to the auditory nerve. Our results demonstrate that
cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type)
potassium current by 50% in chick cochlear hair cells. In contrast, MbetaCD
treatment increased peak inward calcium current (~30%), ruling out loss of
calcium channel expression or function as a cause of reduced calcium-sensitive
outward current. Changes in maximal conductance indicated a direct impact of
cholesterol on channel number or unitary conductance. Immunoblotting following
sucrose-gradient ultracentrifugation revealed BK expression in cholesterol
enriched microdomains. Both direct impacts of cholesterol on channel biophysics,
as well as channel localization in the membrane, may contribute to the influence
of cholesterol on hair cell physiology. Our results reveal a new role for
cholesterol in the regulation of auditory calcium and calcium-activated potassium
channels and add to the growing evidence that cholesterol is a key determinant in
auditory physiology.
PMID- 22046270
TI - Protein kinase C-dependent dephosphorylation of tyrosine hydroxylase requires the
B56delta heterotrimeric form of protein phosphatase 2A.
AB - Tyrosine hydroxylase, which plays a critical role in regulation of dopamine
synthesis, is known to be controlled by phosphorylation at several critical
sites. One of these sites, Ser40, is phosphorylated by a number of protein
kinases, including protein kinase A. The major protein phosphatase that
dephosphorylates Ser40 is protein phosphatase-2A (PP2A). A recent study has also
linked protein kinase C to the dephosphorylation of Ser40 [1], but the mechanism
is unclear. PP2A isoforms are comprised of catalytic, scaffold, and regulatory
subunits, the regulatory B subunits being able to influence cellular localization
and substrate selection. In the current study, we find that protein kinase C is
able to phosphorylate a key regulatory site in the B56delta subunit leading to
activation of PP2A. In turn, activation of the B56delta-containing heterotrimeric
form of PP2A is responsible for enhanced dephosphorylation of Ser40 of tyrosine
hydroylase in response to stimulation of PKC. In support of this mechanism, down
regulation of B56delta expression in N27 cells using RNAi was found to increase
dopamine synthesis. Together these studies reveal molecular details of how
protein kinase C is linked to reduced tyrosine hydroxylase activity via control
of PP2A, and also add to the complexity of protein kinase/protein phosphatase
interactions.
PMID- 22046271
TI - Lung function is associated with arterial stiffness in children.
AB - BACKGROUND: In older adults, an independent association exists between impaired
lung function and cardiovascular disease. This interaction might be related to
the effects of aging and/or smoking. In order to explore possible childhood
antecedents to this association, we hypothesized that decreased lung function and
vascular stiffness might be related, in early life. OBJECTIVE: To determine the
relationship between lung function and carotid augmentation index (AIx), a
measure of vascular stiffness, in 8-year old children. METHODS: Data on brachial
blood pressure, lung function (FEV(1), FVC, FEV(1)/FVC, obtained by spirometry)
and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per
minute, obtained by applanation tonometry) was available in 249 community-based 8
year old children. These healthy children had been subjects in a randomised
controlled trial of two interventions (omega-3 fatty acid supplementation and
house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood
environmental tobacco smoke (ETS) exposure was prospectively collected by
questionnaire. The association between lung function and carotid AIx75 was
assessed in multivariate models that included sex, height, smoking status during
pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and
dietary intervention) as covariates. RESULTS: In the fully adjusted models,
Carotid AIx75 was independently associated with FEV1 (standardised beta = -0.17,b
= -6.72, partial R(2) = .02, p = 0.03), FVC (standardised beta = -0.29, b =
9.31, partial R(2) = 0.04, p<0.001) and FEV1/FVC (standardised beta = .13, b =
18.4, partial R(2) = 0.02, p = 0.04). CONCLUSION: Lower lung volumes are
associated with increased vascular stiffness at an early age. The interaction
between lung function and vascular stiffness may thus represent more than just
age-related alterations in both the pulmonary and vascular systems.
PMID- 22046272
TI - Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic
cells.
AB - Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by
producing large amounts of type I interferon (IFN) by sensing the presence of
viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor
of viral and bacterial DNA motifs and activates the IRF7 transcription factor
which leads to type I IFN secretion by pDCs. However, during chronic hepatitis B
virus (HBV) infection, pDCs display an impaired ability to secrete IFN-alpha
following ex vivo stimulation with TLR9 ligands. Here we highlight several
strategies used by HBV to block IFN-alpha production through a specific
impairment of the TLR9 signaling. Our results show that HBV particle
internalisation could inhibit TLR9- but not TLR7-mediated secretion of IFN-alpha
by pDCs. We observed that HBV down-regulated TLR9 transcriptional activity in
pDCs and B cells in which TLR9 mRNA and protein levels were reduced. HBV can
interfere with TLR9 activity by blocking the MyD88-IRAK4 axis and Sendai virus
targeting IRF7 to block IFN-alpha production. Neutralising CpG motif sequences
were identified within HBV DNA genome of genotypes A to H which displayed a
suppressive effect on TLR9-immune activation. Moreover, TLR9 mRNA and protein
were downregulated in PBMCs from patients with HBV-associated chronic hepatitis
and hepatocellular carcinoma. Thus HBV has developed several escape mechanisms to
avoid TLR9 activation in both pDCs and B lymphocytes, which may in turn
contribute to the establishment and/or persistence of chronic infection.
PMID- 22046274
TI - Continuous three-dimensional control of a virtual helicopter using a motor
imagery based brain-computer interface.
AB - Brain-computer interfaces (BCIs) allow a user to interact with a computer system
using thought. However, only recently have devices capable of providing
sophisticated multi-dimensional control been achieved non-invasively. A major
goal for non-invasive BCI systems has been to provide continuous, intuitive, and
accurate control, while retaining a high level of user autonomy. By employing
electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs)
induced from motor imaginations, a consistent, user-specific control signal may
be characterized. Utilizing a novel method of interactive and continuous control,
we trained three normal subjects to modulate their SMRs to achieve three
dimensional movement of a virtual helicopter that is fast, accurate, and
continuous. In this system, the virtual helicopter's forward-backward translation
and elevation controls were actuated through the modulation of sensorimotor
rhythms that were converted to forces applied to the virtual helicopter at every
simulation time step, and the helicopter's angle of left or right rotation was
linearly mapped, with higher resolution, from sensorimotor rhythms associated
with other motor imaginations. These different resolutions of control allow for
interplay between general intent actuation and fine control as is seen in the
gross and fine movements of the arm and hand. Subjects controlled the helicopter
with the goal of flying through rings (targets) randomly positioned and oriented
in a three-dimensional space. The subjects flew through rings continuously,
acquiring as many as 11 consecutive rings within a five-minute period. In total,
the study group successfully acquired over 85% of presented targets. These
results affirm the effective, three-dimensional control of our motor imagery
based BCI system, and suggest its potential applications in biological
navigation, neuroprosthetics, and other applications.
PMID- 22046273
TI - Absence of colony stimulation factor-1 receptor results in loss of microglia,
disrupted brain development and olfactory deficits.
AB - The brain contains numerous mononuclear phagocytes called microglia. These cells
express the transmembrane tyrosine kinase receptor for the macrophage growth
factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse
strain combined with lineage defining antibody staining we show in the postnatal
mouse brain that CSF-1R is expressed only in microglia and not neurons,
astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a
null mutation in the Csflr gene. In these mice microglia are >99% depleted at
embryonic day 16 and day 1 post-partum brain. At three weeks of age this
microglial depletion continues in most regions of the brain although some contain
clusters of rounded microglia. Despite the loss of microglia, embryonic brain
development appears normal but during the post-natal period the brain
architecture becomes perturbed with enlarged ventricles and regionally compressed
parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the
cortex there is increased neuronal density, elevated numbers of astrocytes but
reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and
therefore to study the role of CSF-1R in olfaction we used the viable null
mutants in the Csf1 (Csf1(op)) gene that encodes one of the two known CSF-1R
ligands. Food-finding experiments indicate that olfactory capacity is
significantly impaired in the absence of CSF-1. CSF-1R is therefore required for
the development of microglia, for a fully functional olfactory system and the
maintenance of normal brain structure.
PMID- 22046275
TI - Reduced distractibility in a remote culture.
AB - BACKGROUND: In visual processing, there are marked cultural differences in the
tendency to adopt either a global or local processing style. A remote culture
(the Himba) has recently been reported to have a greater local bias in visual
processing than Westerners. Here we give the first evidence that a greater, and
remarkable, attentional selectivity provides the basis for this local bias.
METHODOLOGY/PRINCIPAL FINDINGS: In Experiment 1, Eriksen-type flanker
interference was measured in the Himba and in Western controls. In both groups,
responses to the direction of a task-relevant target arrow were affected by the
compatibility of task-irrelevant distractor arrows. However, the Himba showed a
marked reduction in overall flanker interference compared to Westerners. The
smaller interference effect in the Himba occurred despite their overall slower
performance than Westerners, and was evident even at a low level of perceptual
load of the displays. In Experiment 2, the attentional selectivity of the Himba
was further demonstrated by showing that their attention was not even captured by
a moving singleton distractor. CONCLUSIONS/SIGNIFICANCE: We argue that the
reduced distractibility in the Himba is clearly consistent with their tendency to
prioritize the analysis of local details in visual processing.
PMID- 22046276
TI - myKaryoView: a light-weight client for visualization of genomic data.
AB - The Distributed Annotation System (DAS) is a protocol for easy sharing and
integration of biological annotations. In order to visualize feature annotations
in a genomic context a client is required. Here we present myKaryoView, a simple
light-weight DAS tool for visualization of genomic annotation. myKaryoView has
been specifically configured to help analyse data derived from personal genomics,
although it can also be used as a generic genome browser visualization. Several
well-known data sources are provided to facilitate comparison of known genes and
normal variation regions. The navigation experience is enhanced by simultaneous
rendering of different levels of detail across chromosomes. A simple interface is
provided to allow searches for any SNP, gene or chromosomal region. User-defined
DAS data sources may also be added when querying the system. We demonstrate
myKaryoView capabilities for adding user-defined sources with a set of genetic
profiles of family-related individuals downloaded directly from 23andMe.
myKaryoView is a web tool for visualization of genomic data specifically designed
for direct-to-consumer genomic data that uses publicly available data distributed
throughout the Internet. It does not require data to be held locally and it is
capable of rendering any feature as long as it conforms to DAS specifications.
Configuration and addition of sources to myKaryoView can be done through the
interface. Here we show a proof of principle of myKaryoView's ability to display
personal genomics data with 23andMe genome data sources. The tool is available
at: http://mykaryoview.com.
PMID- 22046277
TI - Effects of short-term continuous subcutaneous insulin infusion on fasting plasma
fibroblast growth factor-21 levels in patients with newly diagnosed type 2
diabetes mellitus.
AB - BACKGROUND: To investigate the effects of short-term continuous subcutaneous
insulin infusion (CSII) on plasma fibroblast growth factor-21 (FGF-21) levels in
patients with newly diagnosed type 2 diabetes mellitus (nT2DM). METHOD: Sixty
eight patients with nT2DM (nT2DM group), and 52 gender-, age- and body mass index
(BMI) -matched normal glucose tolerance (NGT group) controls participated in the
study. 30 nT2DM patients with FBG >= 14.0 mmol/L were treated with CSII for 2
weeks, and were underwent a euglycemic-hyperinsulinemic clamp pre- and post
treatment. Plasma FGF-21 concentrations were measured with a commercial ELISA
kit. The relationship between plasma FGF-21 levels and metabolic parameters was
also analyzed. RESULTS: Fasting plasma FGF-21 levels were higher in the nT2DM
group than in NGT groups (1.60 +/- 0.08 vs. 1.13 +/- 0.26 ug/L, P<0.01). In nT2DM
patients, fasting plasma FGF-21 concentrations were significantly decreased after
CSII treatment for 2 weeks (1.60 +/- 0.08 vs.1.30 +/- 0.05 ug/L, P<0.05),
accompanied by a significant increase in the whole body glucose uptake (M value)
and blood glucose control. The changes in plasma FGF-21 levels (DeltaFGF-21) were
positively associated with the amelioration of insulin resistance shown by the
changes in M value. CONCLUSION: Plasma FGF-21 level is associated with whole body
insulin sensitivity and significantly reduced following short-term CSII
treatment.
PMID- 22046278
TI - Loss-of-function of Constitutive Expresser of Pathogenesis Related Genes5 affects
potassium homeostasis in Arabidopsis thaliana.
AB - Here, we demonstrate that the reduction in leaf K(+) observed in a mutant
previously identified in an ionomic screen of fast neutron mutagenized
Arabidopsis thaliana is caused by a loss-of-function allele of CPR5, which we
name cpr5-3. This observation establishes low leaf K(+) as a new phenotype for
loss-of-function alleles of CPR5. We investigate the factors affecting this low
leaf K(+) in cpr5 using double mutants defective in salicylic acid (SA) and
jasmonic acid (JA) signalling, and by gene expression analysis of various
channels and transporters. Reciprocal grafting between cpr5 and Col-0 was used to
determine the relative importance of the shoot and root in causing the low leaf
K(+) phenotype of cpr5. Our data show that loss-of-function of CPR5 in shoots
primarily determines the low leaf K(+) phenotype of cpr5, though the roots also
contribute to a lesser degree. The low leaf K(+) phenotype of cpr5 is independent
of the elevated SA and JA known to occur in cpr5. In cpr5 expression of genes
encoding various Cyclic Nucleotide Gated Channels (CNGCs) are uniquely elevated
in leaves. Further, expression of HAK5, encoding the high affinity K(+) uptake
transporter, is reduced in roots of cpr5 grown with high or low K(+) supply. We
suggest a model in which low leaf K(+) in cpr5 is driven primarily by enhanced
shoot-to-root K(+) export caused by a constitutive activation of the expression
of various CNGCs. This activation may enhance K(+) efflux, either indirectly via
enhanced cytosolic Ca(2+) and/or directly by increased K(+) transport activity.
Enhanced shoot-to-root K(+) export may also cause the reduced expression of HAK5
observed in roots of cpr5, leading to a reduction in uptake of K(+). All ionomic
data presented is publically available at www.ionomicshub.org.
PMID- 22046279
TI - Carbon monoxide induced PPARgamma SUMOylation and UCP2 block inflammatory gene
expression in macrophages.
AB - Carbon monoxide (CO) dampens pro-inflammatory responses in a peroxisome
proliferator-activated receptor-gamma (PPARgamma) and p38 mitogen-activated
protein kinase (MAPK) dependent manner. Previously, we demonstrated that CO
inhibits lipopolysaccharide (LPS)-induced expression of the proinflammatory early
growth response-1 (Egr-1) transcription factor in macrophages via activation of
PPARgamma. Here, we further characterize the molecular mechanisms by which CO
modulates the activity of PPARgamma and Egr-1 repression. We demonstrate that CO
enhances SUMOylation of PPARgamma which we find was attributed to mitochondrial
ROS generation. Ectopic expression of a SUMOylation-defective PPARgamma-K365R
mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter
activity. Expression of a PPARgamma-K77R mutant did not impair the effect of CO.
In addition to PPARgamma SUMOylation, CO-activated p38 MAPK was responsible for
Egr-1 repression. Blocking both CO-induced PPARgamma SUMOylation and p38
activation, completely reversed the effects of CO on inflammatory gene
expression. In primary macrophages isolated form C57/BL6 male mice, we identify
mitochondrial ROS formation by CO as the upstream trigger for the observed
effects on Egr-1 in part through uncoupling protein 2 (UCP2). Macrophages derived
from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-)),
produced significantly less ROS with CO exposure versus wild-type macrophages.
Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1
repression. Collectively, these results indentify p38 activation, PPARgamma
SUMOylation and ROS formation via UCP2 as a cooperative system by which CO
impacts the inflammatory response.
PMID- 22046280
TI - Non-invasive cytology brush PCR diagnostic testing in mucosal leishmaniasis:
superior performance to conventional biopsy with histopathology.
AB - BACKGROUND: Traditional methods of diagnosing mucosal leishmaniasis (ML), such as
biopsy with histopathology, are insensitive and require collection of an invasive
diagnostic specimen. METHODS: We compared standard invasive procedures including
biopsy histopathology, biopsy PCR, and leishmanin skin test (LST) to a novel, non
invasive, cytology-brush based PCR for the diagnosis of ML in Lima, Peru.
Consensus reference standard was 2/4 tests positive, and outcome measures were
sensitivity and specificity. Leishmania species identification was performed by
PCR-based assays of positive specimens. RESULTS: Twenty-eight patients were
enrolled, 23 of whom fulfilled criteria for a diagnosis of ML. Sensitivity and
specificity of biopsy with histopathology were 21.7% [95% CI 4.9-38.5%] and 100%;
69.6% [95% CI 50.8-88.4%] and 100% for LST; 95.7% [95% CI 87.4-100%] and 100% for
biopsy PCR; and 95.7% [95% CI 87.4-100%] and 90% [95% CI 71.4-100%] for cytology
brush PCR using both Cervisoft(r) and Histobrush(r) cervical cytology brushes.
Represented species identified by PCR-RFLP included: L. (V). braziliensis (n =
4), and L. (V). peruviana (n = 3). CONCLUSIONS: Use of commercial grade cytology
brush PCR for diagnosis of ML is sensitive, rapid, well tolerated, and carries
none of the risks of invasive diagnostic procedures such as biopsy. Further
optimization is required for adequate species identification. Further evaluation
of this method in field and other settings is warranted.
PMID- 22046281
TI - Increased feeding and food hoarding following food deprivation are associated
with activation of dopamine and orexin neurons in male Brandt's voles.
AB - Small mammals usually face energetic challenges, such as food shortage, in the
field. They have thus evolved species-specific adaptive strategies for survival
and reproductive success. In the present study, we examined male Brandt's voles
(Lasiopodomys brandtii) for their physiological, behavioral, and neuronal
responses to food deprivation (FD) and subsequent re-feeding. Although 48 hr FD
induced a decrease in body weight and the resting metabolic rate (RMR), such
decreases did not reach statistical significance when compared to the control
males that did not experience FD. During the first 2 hr of re-feeding following
48 hr FD, voles showed higher levels of feeding than controls. However, when
permitted to hoard food, FD voles showed an increase in food hoarding, rather
than feeding, compared to the controls. Further, both feeding and food hoarding
induced an increase in neuronal activation, measured by Fos-ir, in a large number
of brain areas examined. Interestingly, feeding and food hoarding also induced an
increase in the percentage of tyrosine hydroxylase immunoreactive (TH-ir) cells
that co-expressed Fos-ir in the ventral tegmental area (VTA), whereas both FD and
feeding induced an increase in the percentage of orexin-ir cells that co
expressed Fos-ir in the lateral hypothalamus (LH). Food hoarding also increased
orexin-ir/Fos-ir labeling in the LH. Together, our data indicate that food
deprived male Brandt's voles display enhanced feeding or food hoarding dependent
upon an environmental setting. In addition, changes in central dopamine and
orexin activities in selected brain areas are associated with feeding and
hoarding behaviors following FD and subsequent re-feeding.
PMID- 22046282
TI - Silencing GADD153/CHOP gene expression protects against Alzheimer's disease-like
pathology induced by 27-hydroxycholesterol in rabbit hippocampus.
AB - Endoplasmic reticulum (ER) stress is suggested to play a key role in the
pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD).
Sustained ER stress leads to activation of the growth arrest and leucine zipper
transcription factor, DNA damage inducible gene 153 (gadd153; also called CHOP).
Activated gadd153 can generate oxidative damage and reactive oxygen species
(ROS), increase beta-amyloid (Abeta) levels, disturb iron homeostasis and induce
inflammation as well as cell death, which are all pathological hallmarks of AD.
Epidemiological and laboratory studies suggest that cholesterol dyshomeostasis
contributes to the pathogenesis of AD. We have previously shown that the
cholesterol oxidized metabolite 27-hydroxycholesterol (27-OHC) triggers AD-like
pathology in organotypic slices. However, the extent to which gadd153 mediates 27
OHC effects has not been determined. We silenced gadd153 gene with siRNA and
determined the effects of 27-OHC on AD hallmarks in organotypic slices from adult
rabbit hippocampus. siRNA to gadd153 reduced 27-OHC-induced Abeta production by
mechanisms involving reduction in levels of beta-amyloid precursor protein (APP)
and beta-secretase (BACE1), the enzyme that initiates cleavage of APP to yield
Abeta peptides. Additionally, 27-OHC-induced tau phosphorylation, ROS generation,
TNF-alpha activation, and iron and apoptosis-regulatory protein levels alteration
were also markedly reduced by siRNA to gadd153. These data suggest that ER stress
mediated gadd153 activation plays a central role in the triggering of AD
pathological hallmarks that result from incubation of hippocampal slices with 27
OHC. Our results add important insights into cellular mechanisms that underlie
the potential contribution of cholesterol metabolism in AD pathology, and suggest
that preventing gadd153 activation protects against AD related to cholesterol
oxidized products.
PMID- 22046283
TI - Assessing the cost of helping: the roles of body condition and oxidative balance
in the Seychelles warbler (Acrocephalus sechellensis).
AB - In cooperatively breeding species, helping close relatives may provide important
fitness benefits. However, helping can be energetically expensive and may result
in increased generation of reactive oxygen species. Consequently, an
oxidant/antioxidant imbalance can lead to higher oxidative stress susceptibility.
Given the potential costs of helping, it may be that only individuals with a
sufficiently good body condition and/or stable oxidative balance can afford to
help. Knowledge about relationships between social status and oxidative balance
in cooperatively breeding systems is still limited. Studying these relationships
is important for understanding the costs of helping and physiological pressures
of reproduction. Here we evaluate the relationship between helping behaviour,
body condition and oxidative balance in a wild population of the cooperatively
breeding Seychelles warbler (Acrocephalus sechellensis). In this species, some
subordinate individuals help dominant birds with the rearing of young, while
others refrain from any assistance. We assessed body condition and oxidative
parameters of birds of different social status caught during different breeding
stages. We found that, prior to breeding, female subordinates that did not
subsequently help (non-helpers) had significantly lower body condition and higher
ROMs (reactive oxygen metabolites) than helpers and dominants. During the later
stages of breeding, body condition was low in dominants and helpers, but high in
non-helpers. Differences in oxidative balance between individuals of different
social status were found only during nest care: Dominant males occupied with
guarding behaviours tended to have relatively high oxidative stress
susceptibility. Furthermore, dominant and helper females showed elevated
antioxidant capacity (measured as OXY) in the weeks just prior to egg-laying,
possibly representing a change in their reproductive physiology. The results
imply that an individuals' oxidative balance may be influenced by factors related
to reproduction, which can differ with sex and--within cooperative breeding
systems--social status.
PMID- 22046284
TI - Scatter-hoarding rodents prefer slightly astringent food.
AB - The mutualistic interaction between scatter-hoarding rodents and their seed
plants is highly complex yet poorly understood. Plants may benefit from the seed
dispersal behavior of rodents, as long as seed consumption is minimized. In
parallel, rodents may maximize foraging efficiency and cache high-quality
resources for future consumption. Defensive compounds, such as tannins, are
thought to be a major mechanism for plant control over rodent behavior. However,
previous studies, using naturally occurring seeds, have not provided conclusive
evidence supporting this hypothesis. Here, we test the importance of tannin
concentrations on the scatter-hoarding behavior of rodents by using an artificial
seed system. We combined feeding trials and field observations to examine the
overall impact of seed tannin concentrations on rodent behavior and health. We
found that rodents favored seeds with an intermediate amount of tannin (~5%) in
the field. Meanwhile, in rodents that were fed a diet with different tannin
content, only diets with high tannin content (25%, 15%, and 10%) caused a
significant negative influence on rodent survival and health. Significant
differences were not found among treatments with tannin levels of 0-5%. In
contrast to many existing studies, our results clearly demonstrate that scatter
hoarding rodents prefer slightly 'astringent' food. In the co-evolutionary arms
race between plants and animals, our results suggest that while tannins may play
a significant role in reducing general predation levels by the faunal community,
they have no precise control over the behavior of their mutualistic partner.
Instead, the two partners appear to have reached an evolutionary point where both
parties receive adequate benefits, with the year-to-year outcome being dependent
on a wide range of factors beyond the control of either partner.
PMID- 22046285
TI - Identification of antigens specific to non-tuberculous mycobacteria: the Mce
family of proteins as a target of T cell immune responses.
AB - The lack of an effective TB vaccine hinders current efforts in combating the TB
pandemic. One theory as to why BCG is less protective in tropical countries is
that exposure to non-tuberculous mycobacteria (NTM) reduces BCG efficacy. There
are currently several new TB vaccines in clinical trials, and NTM exposure may
also be relevant in this context. NTM exposure cannot be accurately evaluated in
the absence of specific antigens; those which are known to be present in NTM and
absent from M. tuberculosis and BCG. We therefore used a bioinformatic pipeline
to define proteins which are present in common NTM and absent from the M.
tuberculosis complex, using protein BLAST, TBLASTN and a short sequence protein
BLAST to ensure the specificity of this process. We then assessed immune
responses to these proteins, in healthy South Africans and in patients from the
United Kingdom and United States with documented exposure to NTM. Low level
responses were detected to a cluster of proteins from the mammalian cell entry
family, and to a cluster of hypothetical proteins, using ex vivo ELISpot and a 6
day proliferation assay. These early findings may provide a basis for
characterising exposure to NTM at a population level, which has applications in
the field of TB vaccine design as well as in the development of diagnostic tests.
PMID- 22046286
TI - A novel evolution-based method for detecting gene-gene interactions.
AB - BACKGROUND: The rapid advance in large-scale SNP-chip technologies offers us
great opportunities in elucidating the genetic basis of complex diseases. Methods
for large-scale interactions analysis have been under development from several
sources. Due to several difficult issues (e.g., sparseness of data in high
dimensions and low replication or validation rate), development of fast, powerful
and robust methods for detecting various forms of gene-gene interactions
continues to be a challenging task. METHODOLOGY/PRINCIPAL FINDINGS: In this
article, we have developed an evolution-based method to search for genome-wide
epistasis in a case-control design. From an evolutionary perspective, we view
that human diseases originate from ancient mutations and consider that the
underlying genetic variants play a role in differentiating human population into
the healthy and the diseased. Based on this concept, traditional evolutionary
measure, fixation index (Fst) for two unlinked loci, which measures the genetic
distance between populations, should be able to reveal the responsible genetic
interplays for disease traits. To validate our proposal, we first investigated
the theoretical distribution of Fst by using extensive simulations. Then, we
explored its power for detecting gene-gene interactions via SNP markers, and
compared it with the conventional Pearson Chi-square test, mutual information
based test and linkage disequilibrium based test under several disease models.
The proposed evolution-based method outperformed these compared methods in
dominant and additive models, no matter what the disease allele frequencies were.
However, its performance was relatively poor in a recessive model. Finally, we
applied the proposed evolution-based method to analysis of a published dataset.
Our results showed that the P value of the Fst -based statistic is smaller than
those obtained by the LD-based statistic or Poisson regression models.
CONCLUSIONS/SIGNIFICANCE: With rapidly growing large-scale genetic association
studies, the proposed evolution-based method can be a promising tool in the
identification of epistatic effects.
PMID- 22046287
TI - Molecular diversity of fungal phylotypes co-amplified alongside nematodes from
coastal and deep-sea marine environments.
AB - Nematodes and fungi are both ubiquitous in marine environments, yet few studies
have investigated relationships between these two groups. Microbial species share
many well-documented interactions with both free-living and parasitic nematode
species, and limited data from previous studies have suggested ecological
associations between fungi and nematodes in benthic marine habitats. This study
aimed to further document the taxonomy and distribution of fungal taxa often co
amplified from nematode specimens. A total of 15 fungal 18S rRNA phylotypes were
isolated from nematode specimens representing both deep-sea and shallow water
habitats; all fungal isolates displayed high pairwise sequence identities with
published data in Genbank (99-100%) and unpublished high-throughput 454
environmental datasets (>95%). BLAST matches indicate marine fungal sequences
amplified in this study broadly represent taxa within the phyla Ascomycota and
Basidiomycota, and several phylotypes showed robust groupings with known taxa in
phylogenetic topologies. In addition, some fungal phylotypes appeared to be
present in disparate geographic habitats, suggesting cosmopolitan distributions
or closely related species complexes in at least some marine fungi. The present
study was only able to isolate fungal DNA from a restricted set of nematode taxa;
further work is needed to fully investigate the taxonomic scope and function of
nematode-fungal interactions.
PMID- 22046288
TI - Multichannel detrended fluctuation analysis reveals synchronized patterns of
spontaneous spinal activity in anesthetized cats.
AB - The analysis of the interaction and synchronization of relatively large ensembles
of neurons is fundamental for the understanding of complex functions of the
nervous system. It is known that the temporal synchronization of neural ensembles
is involved in the generation of specific motor, sensory or cognitive processes.
Also, the intersegmental coherence of spinal spontaneous activity may indicate
the existence of synaptic neural pathways between different pairs of lumbar
segments. In this study we present a multichannel version of the detrended
fluctuation analysis method (mDFA) to analyze the correlation dynamics of
spontaneous spinal activity (SSA) from time series analysis. This method together
with the classical detrended fluctuation analysis (DFA) were used to find out
whether the SSA recorded in one or several segments in the spinal cord of the
anesthetized cat occurs either in a random or in an organized manner. Our results
are consistent with a non-random organization of the sets of neurons involved in
the generation of spontaneous cord dorsum potentials (CDPs) recorded either from
one lumbar segment (DFA-alpha mean = 1.04[Formula: see text]0.09) or
simultaneously from several lumbar segments (mDFA-alpha mean = 1.01[Formula: see
text]0.06), where alpha = 0.5 indicates randomness while alpha = 0.5 indicates
long-term correlations. To test the sensitivity of the mDFA method we also
examined the effects of small spinal lesions aimed to partially interrupt
connectivity between neighboring lumbosacral segments. We found that the
synchronization and correlation between the CDPs recorded from the L5 and L6
segments in both sides of the spinal cord were reduced when a lesion comprising
the left dorsal quadrant was performed between the segments L5 and L6 (mDFA
[Formula: see text] = 0.992 as compared to initial conditions mDFA-alpha =
1.186). The synchronization and correlation were reduced even further after a
similar additional right spinal lesion (mDFA-alpha = 0.924). In contrast to the
classical methods, such as correlation and coherence quantification that define a
relation between two sets of data, the mDFA method properly reveals the
synchronization of multiple groups of neurons in several segments of the spinal
cord. This method is envisaged as a useful tool to characterize the structure of
higher order ensembles of cord dorsum spontaneous potentials after spinal cord or
peripheral nerve lesions.
PMID- 22046289
TI - The nature and perception of fluctuations in human musical rhythms.
AB - Although human musical performances represent one of the most valuable
achievements of mankind, the best musicians perform imperfectly. Musical rhythms
are not entirely accurate and thus inevitably deviate from the ideal beat
pattern. Nevertheless, computer generated perfect beat patterns are frequently
devalued by listeners due to a perceived lack of human touch. Professional audio
editing software therefore offers a humanizing feature which artificially
generates rhythmic fluctuations. However, the built-in humanizing units are
essentially random number generators producing only simple uncorrelated
fluctuations. Here, for the first time, we establish long-range fluctuations as
an inevitable natural companion of both simple and complex human rhythmic
performances. Moreover, we demonstrate that listeners strongly prefer long-range
correlated fluctuations in musical rhythms. Thus, the favorable fluctuation type
for humanizing interbeat intervals coincides with the one generically inherent in
human musical performances.
PMID- 22046290
TI - Impact of definitive therapy with beta-lactam monotherapy or combination with an
aminoglycoside or a quinolone for Pseudomonas aeruginosa bacteremia.
AB - BACKGROUND: Bacteremia by Pseudomonas aeruginosa represents one severe infection.
It is not clear whether beta-lactam monotherapy leads to similar rates of
treatment success compared to combinations of beta-lactams with aminoglycosides
or quinolones. METHODS: Retrospective cohort study from 3 tertiary hospitals (2
in Greece and 1 in Italy). Pseudomonas aeruginosa isolates were susceptible to a
beta-lactam and an aminoglycoside or a quinolone. Patients received appropriate
therapy for at least 48 hours. Primary outcome of interest was treatment success
in patients with definitive beta-lactam combination therapy compared to
monotherapy. Secondary outcomes were treatment success keeping the same empirical
and definitive regimen, mortality, and toxicity. RESULTS: Out of 92 bacteremias
there were 54 evaluable episodes for the primary outcome (20 received
monotherapy). Treatment success was higher with combination therapy (85%)
compared to beta-lactam monotherapy (65%), however not statistically
significantly [Odds ratio (OR) 3.1; 95% Confidence Interval (CI) 0.69-14.7, p =
0.1]. Very long (>2 months) hospitalisation before bacteremia was the only factor
independently associated with treatment success (OR 0.73; 95% CI 0.01-0.95, p =
0.046), however this result entailed few episodes. All-cause mortality did not
differ significantly between combination therapy [6/31 (19%)] and monotherapy
[8/19 (42%)], p = 0.11. Only Charlson comorbidity index was associated with
excess mortality (p = 0.03). CONCLUSION: Our study, in accordance with previous
ones, indicates that the choice between monotherapy and combination therapy may
not affect treatment success significantly. However, our study does not have
statistical power to identify small or moderate differences. A large randomized
controlled trial evaluating this issue is justified.
PMID- 22046291
TI - Effect of DNA groove binder distamycin A upon chromatin structure.
AB - BACKGROUND: Distamycin A is a prototype minor groove binder, which binds to B
form DNA, preferentially at A/T rich sites. Extensive work in the past few
decades has characterized the binding at the level of double stranded DNA.
However, effect of the same on physiological DNA, i.e. DNA complexed in
chromatin, has not been well studied. Here we elucidate from a structural
perspective, the interaction of distamycin with soluble chromatin, isolated from
Sprague-Dawley rat. METHODOLOGY/PRINCIPAL FINDINGS: Chromatin is a hierarchical
assemblage of DNA and protein. Therefore, in order to characterize the
interaction of the same with distamycin, we have classified the system into
various levels, according to the requirements of the method adopted, and the
information to be obtained. Isothermal titration calorimetry has been employed to
characterize the binding at the levels of chromatin, chromatosome and chromosomal
DNA. Thermodynamic parameters obtained thereof, identify enthalpy as the driving
force for the association, with comparable binding affinity and free energy for
chromatin and chromosomal DNA. Reaction enthalpies at different temperatures were
utilized to evaluate the change in specific heat capacity (DeltaCp), which, in
turn, indicated a possible binding associated structural change. Ligand induced
structural alterations have been monitored by two complementary methods--dynamic
light scattering, and transmission electron microscopy. They indicate compaction
of chromatin. Using transmission electron microscopy, we have visualized the
effect of distamycin upon chromatin architecture at di- and trinucleosome levels.
Our results elucidate the simultaneous involvement of linker bending and
internucleosomal angle contraction in compaction process induced by distamycin.
CONCLUSIONS/SIGNIFICANCE: We summarize here, for the first time, the
thermodynamic parameters for the interaction of distamycin with soluble
chromatin, and elucidate its effect on chromatin architecture. The study provides
insight into a ligand induced compaction phenomenon, and suggests new mechanisms
of chromatin architectural alteration.
PMID- 22046292
TI - Physiological phenomenology of neurally-mediated syncope with management
implications.
AB - BACKGROUND: Due to lack of efficacy in recent trials, current guidelines for the
treatment of neurally-mediated (vasovagal) syncope do not promote cardiac
pacemaker implantation. However, the finding of asystole during head-up tilt
induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and
treatment with cardiac pacemakers as blood pressure is often discontinuously
measured. Furthermore, physicians may be more inclined to implant cardiac
pacemakers in older patients. We hypothesized that true cardioinhibitory syncope
in which the decrease in heart rate precedes the fall in blood pressure is a very
rare finding which might explain the lack of efficacy of pacemakers in neurally
mediated syncope. METHODS: We studied 173 consecutive patients referred for
unexplained syncope (114 women, 59 men, 42 +/- 1 years, 17 +/- 2 syncopal
episodes). All had experienced (pre)syncope during head-up tilt testing followed
by additional lower body negative suction. We classified hemodynamic responses
according to the modified Vasovagal Syncope International Study (VASIS)
classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa)
or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the
exact temporal relationship between hypotension and bradycardia to identify
patients with true cardioinhibitory syncope. RESULTS: Of the (pre)syncopal events
during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS
IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II)
progressively decreased from the youngest to the oldest age quartile. With more
detailed temporal analysis, blood pressure reduction preceded the heart-rate
decrease in all but six individuals (97%) overall and in 10 out of 11 patients
with asystole (VASIS IIb). CONCLUSIONS: Hypotension precedes bradycardia onset
during head-up tilt-induced (pre)syncope in the vast majority of patients, even
in those classified as cardioinhibitory syncope according to the modified VASIS
classification. Furthermore, cardioinhibitory syncope becomes less frequent with
increasing age.
PMID- 22046293
TI - Why do woodpeckers resist head impact injury: a biomechanical investigation.
AB - Head injury is a leading cause of morbidity and death in both industrialized and
developing countries. It is estimated that brain injuries account for 15% of the
burden of fatalities and disabilities, and represent the leading cause of death
in young adults. Brain injury may be caused by an impact or a sudden change in
the linear and/or angular velocity of the head. However, the woodpecker does not
experience any head injury at the high speed of 6-7 m/s with a deceleration of
1000 g when it drums a tree trunk. It is still not known how woodpeckers protect
their brain from impact injury. In order to investigate this, two synchronous
high-speed video systems were used to observe the pecking process, and the force
sensor was used to measure the peck force. The mechanical properties and
macro/micro morphological structure in woodpecker's head were investigated using
a mechanical testing system and micro-CT scanning. Finite element (FE) models of
the woodpecker's head were established to study the dynamic intracranial
responses. The result showed that macro/micro morphology of cranial bone and beak
can be recognized as a major contributor to non-impact-injuries. This
biomechanical analysis makes it possible to visualize events during woodpecker
pecking and may inspire new approaches to prevention and treatment of human head
injury.
PMID- 22046294
TI - Protective CD8 memory T cell responses to mouse melanoma are generated in the
absence of CD4 T cell help.
AB - BACKGROUND: We have previously demonstrated that temporary depletion of CD4 T
cells in mice with progressive B16 melanoma, followed by surgical tumor excision,
induces protective memory CD8 T cell responses to melanoma/melanocyte antigens.
We also showed that persistence of these CD8 T cells is supported, in an antigen
dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we
explore the requirement of CD4 T cell help in priming and maintaining this
protective CD8 T cell response to melanoma. METHODOLOGY AND PRINCIPAL FINDINGS:
To induce melanoma/melanocyte antigen-specific CD8 T cells, B16 tumor bearing
mice were depleted of regulatory T cells (T(reg)) by either temporary, or long
term continuous treatment with anti-CD4 (mAb clone GK1.5). Total depletion of CD4
T cells led to significant priming of IFN-gamma-producing CD8 T cell responses to
TRP-2 and gp100. Surprisingly, treatment with anti-CD25 (mAb clone PC61), to
specifically deplete T(reg) cells while leaving help intact, was ineffective at
priming CD8 T cells. Thirty to sixty days after primary tumors were surgically
excised, mice completely lacking CD4 T cell help developed autoimmune vitiligo,
and maintained antigen-specific memory CD8 T cell responses that were highly
effective at producing cytokines (IFN-gamma, TNF-alpha, and IL-2). Mice lacking
total CD4 T cell help also mounted protection against re-challenge with B16
melanoma sixty days after primary tumor excision. CONCLUSIONS AND SIGNIFICANCE:
This work establishes that CD4 T cell help is dispensable for the generation of
protective memory T cell responses to melanoma. Our findings support further use
of CD4 T cell depletion therapy for inducing long-lived immunity to cancer.
PMID- 22046295
TI - Differential roles of hyperglycemia and hypoinsulinemia in diabetes induced
retinal cell death: evidence for retinal insulin resistance.
AB - Diabetes pathology derives from the combination of hyperglycemia and
hypoinsulinemia or insulin resistance leading to diabetic complications including
diabetic neuropathy, nephropathy and retinopathy. Diabetic retinopathy is
characterized by numerous retinal defects affecting the vasculature and the neuro
retina, but the relative contributions of the loss of retinal insulin signaling
and hyperglycemia have never been directly compared. In this study we tested the
hypothesis that increased retinal insulin signaling and glycemic normalization
would exert differential effects on retinal cell survival and retinal physiology
during diabetes. We have demonstrated in this study that both subconjunctival
insulin administration and systemic glycemic reduction using the sodium-glucose
linked transporter inhibitor phloridzin affected the regulation of retinal cell
survival in diabetic rats. Both treatments partially restored the retinal insulin
signaling without increasing plasma insulin levels. Retinal transcriptomic and
histological analysis also clearly demonstrated that local administration of
insulin and systemic glycemia normalization use different pathways to counteract
the effects of diabetes on the retina. While local insulin primarily affected
inflammation-associated pathways, systemic glycemic control affected pathways
involved in the regulation of cell signaling and metabolism. These results
suggest that hyperglycemia induces resistance to growth factor action in the
retina and clearly demonstrate that both restoration of glycemic control and
retinal insulin signaling can act through different pathways to both normalize
diabetes-induced retinal abnormality and prevent vision loss.
PMID- 22046296
TI - An integrated analysis of miRNA and mRNA expressions in non-small cell lung
cancers.
AB - Using DNA microarrays, we generated both mRNA and miRNA expression data from 6
non-small cell lung cancer (NSCLC) tissues and their matching normal control from
adjacent tissues to identify potential miRNA markers for diagnostics. We
demonstrated that hsa-miR-96 is significantly and consistently up-regulated in
all 6 NSCLCs. We validated this result in an independent set of 35 paired tumors
and their adjacent normal tissues, as well as their sera that are collected
before surgical resection or chemotherapy, and the results suggested that hsa-miR
96 may play an important role in NSCLC development and has great potential to be
used as a noninvasive marker for diagnosing NSCLC. We predicted potential miRNA
target mRNAs based on different methods (TargetScan and miRanda). Further
classification of miRNA regulated genes based on their relationship with miRNAs
revealed that hsa-miR-96 and certain other miRNAs tend to down-regulate their
target mRNAs in NSCLC development, which have expression levels permissive to
direct interaction between miRNAs and their target mRNAs. In addition, we
identified a significant correlation of miRNA regulation with genes coincide with
high density of CpG islands, which suggests that miRNA may represent a primary
regulatory mechanism governing basic cellular functions and cell
differentiations, and such mechanism may be complementary to DNA methylation in
repressing or activating gene expression.
PMID- 22046297
TI - Sensory coding by cerebellar mossy fibres through inhibition-driven phase
resetting and synchronisation.
AB - Temporal coding of spike-times using oscillatory mechanisms allied to spike-time
dependent plasticity could represent a powerful mechanism for neuronal
communication. However, it is unclear how temporal coding is constructed at the
single neuronal level. Here we investigate a novel class of highly regular,
metronome-like neurones in the rat brainstem which form a major source of
cerebellar afferents. Stimulation of sensory inputs evoked brief periods of
inhibition that interrupted the regular firing of these cells leading to phase
shifted spike-time advancements and delays. Alongside phase-shifting, metronome
cells also behaved as band-pass filters during rhythmic sensory stimulation, with
maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic
firing frequency of each neurone. Phase-shifting and band-pass filtering serve to
temporally align ensembles of metronome cells, leading to sustained volleys of
near-coincident spike-times, thereby transmitting synchronised sensory
information to downstream targets in the cerebellar cortex.
PMID- 22046298
TI - Overexpression of active Aurora-C kinase results in cell transformation and
tumour formation.
AB - Aurora kinases belong to a conserved family of serine/threonine kinases key
regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in
somatic cells and involved mainly in mitosis while Aurora-C is expressed during
spermatogenesis and oogenesis and is involved in meiosis. Aurora-C is hardly
detectable in normal somatic cells. However all three kinases are overexpressed
in many cancer lines. Aurora-A possesses an oncogenic activity while Aurora-B
does not. Here we investigated whether Aurora-C possesses such an oncogenic
activity. We report that overexpression of Aurora-C induces abnormal cell
division resulting in centrosome amplification and multinucleation in both
transiently transfected cells and in stable cell lines. Only stable NIH3T3 cell
clones overexpressing active Aurora-C formed foci of colonies when grown on soft
agar, indicating that a gain of Aurora-C activity is sufficient to transform
cells. Furthermore, we reported that NIH-3T3 stable cell lines overexpressing
Aurora-C induced tumour formation when injected into nude mice, demonstrating the
oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough
tumor aggressiveness was positively correlated with the quantity of active
kinase, making Aurora-C a potential anti-cancer therapeutic target.
PMID- 22046299
TI - Profiling of Burkholderia cepacia secretome at mid-logarithmic and early
stationary phases of growth.
AB - BACKGROUND: Burkholderia cepacia is a Gram-negative pathogen that causes serious
respiratory infections in immunocompromised patients and individuals with cystic
fibrosis. This bacterium is known to release extracellular proteins that may be
involved in virulence. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, B.
cepacia grown to mid-logarithmic and early-stationary phases were investigated on
their ability to invade and survive intracellularly in A549 lung epithelial cells
in order to discern the fate of these bacteria in the pathogenesis of B. cepacia
lung infections in in vitro condition. The early-stationary phase B. cepacia was
demonstrated to be more invasive than mid-logarithmic phase. In addition, culture
supernatants of B. cepacia obtained from these phases of growth were also
demonstrated to cause different cytotoxic potency on the A549 human lung
epithelial cells. Profiling of the supernatants using the gel-based proteomics
approach identified 43 proteins that were commonly released in both the growth
phases and 40 proteins newly-released at the early-stationary phase. The latter
proteins may account for the higher cytotoxic activity of the early-stationary
culture supernatant compared to that obtained at the mid-logarithmic phase. Among
the newly-released proteins in the early-stationary phase supernatant were
flagellar hook-associated domain protein (FliD), flagellar hook-associated
protein (FlgK), TonB-dependent siderophore (Fiu), Elongation factor G (FusA),
phosphoglycerate kinase (Pgk) and sulfatase (AslA) which are known for their
virulence. CONCLUSION/SIGNIFICANCE: Differences in the ability of B. cepacia to
invade and survive intracellularly inside the epithelial cells at different
phases of growth may improve our understanding of the varied disease progressions
associated with B. cepacia infections. In addition, the identified culture
supernatant proteins may be used as targets for the development of new strategies
to control B. cepacia infection using agents that can block their release.
PMID- 22046300
TI - miRConnect: identifying effector genes of miRNAs and miRNA families in cancer
cells.
AB - micro(mi)RNAs are small non-coding RNAs that negatively regulate expression of
most mRNAs. They are powerful regulators of various differentiation stages, and
the expression of genes that either negatively or positively correlate with
expressed miRNAs is expected to hold information on the biological state of the
cell and, hence, of the function of the expressed miRNAs. We have compared the
large amount of available gene array data on the steady state system of the NCI60
cell lines to two different data sets containing information on the expression of
583 individual miRNAs. In addition, we have generated custom data sets containing
expression information of 54 miRNA families sharing the same seed match. We have
developed a novel strategy for correlating miRNAs with individual genes based on
a summed Pearson Correlation Coefficient (sPCC) that mimics an in silico
titration experiment. By focusing on the genes that correlate with the expression
of miRNAs without necessarily being direct targets of miRNAs, we have clustered
miRNAs into different functional groups. This has resulted in the identification
of three novel miRNAs that are linked to the epithelial-to-mesenchymal transition
(EMT) in addition to the known EMT regulators of the miR-200 miRNA family. In
addition, an analysis of gene signatures associated with EMT, c-MYC activity, and
ribosomal protein gene expression allowed us to assign different activities to
each of the functional clusters of miRNAs. All correlation data are available via
a web interface that allows investigators to identify genes whose expression
correlates with the expression of single miRNAs or entire miRNA families.
miRConnect.org will aid in identifying pathways regulated by miRNAs without
requiring specific knowledge of miRNA targets.
PMID- 22046301
TI - Effect of rickettsial toxin VapC on its eukaryotic host.
AB - Rickettsia are intracellular bacteria typically associated with arthropods that
can be transmitted to humans by infected vectors. Rickettsia spp. can cause mild
to severe human disease with a possible protection effect of corticosteroids when
antibiotic treatments are initiated. We identified laterally transferred toxin
antitoxin (TA) genetic elements, including vapB/C, in several Rickettsia genomes
and showed that they are functional in bacteria and eukaryotic cells. We also
generated a plaque assay to monitor the formation of lytic plaques over time and
demonstrated that chloramphenicol accelerates host cell lysis of vapB/C
containing Rickettsia. Whole-genome expression, TUNEL and FISH assays on the
infected cells following exposure to the antibiotic revealed early apoptosis of
host cells, which was linked to over-transcription of bacterial vapB/C operons
and subsequent cytoplasmic VapC toxin release. VapC that is expressed in
Escherichia coli and Saccharomyces cerevisiae or microinjected into mammalian
cells is toxic through RNase activity and is prevented by dexamethasone. This
study provides the first biological evidence that toxin-antitoxin elements act as
pathogenic factors in bacterial host cells, confirming comparative genomic
evidence of their role in bacterial pathogenicity. Our results suggest that early
mortality following antibiotic treatment of some bacterial infections can be
prevented by administration of dexamethasone.
PMID- 22046302
TI - Assessing the impacts of experimentally elevated temperature on the biological
composition and molecular chaperone gene expression of a reef coral.
AB - Due to the potential for increasing ocean temperatures to detrimentally impact
reef-building corals, there is an urgent need to better understand not only the
coral thermal stress response, but also natural variation in their sub-cellular
composition. To address this issue, while simultaneously developing a molecular
platform for studying one of the most common Taiwanese reef corals, Seriatopora
hystrix, 1,092 cDNA clones were sequenced and characterized. Subsequently, RNA,
DNA and protein were extracted sequentially from colonies exposed to elevated (30
degrees C) temperature for 48 hours. From the RNA phase, a heat shock protein-70
(hsp70)-like gene, deemed hsp/c, was identified in the coral host, and expression
of this gene was measured with real-time quantitative PCR (qPCR) in both the host
anthozoan and endosymbiotic dinoflagellates (genus Symbiodinium). While mRNA
levels were not affected by temperature in either member, hsp/c expression was
temporally variable in both and co-varied within biopsies. From the DNA phase,
host and Symbiodinium hsp/c genome copy proportions (GCPs) were calculated to
track changes in the biological composition of the holobiont during the
experiment. While there was no temperature effect on either host or Symbiodinium
GCP, both demonstrated significant temporal variation. Finally, total soluble
protein was responsive to neither temperature nor exposure time, though the
protein/DNA ratio varied significantly over time. Collectively, it appears that
time, and not temperature, is a more important driver of the variation in these
parameters, highlighting the need to consider natural variation in both gene
expression and the molecular make-up of coral holobionts when conducting
manipulative studies. This represents the first study to survey multiple
macromolecules from both compartments of an endosymbiotic organism with
methodologies that reflect their dual-compartmental nature, ideally generating a
framework for assessing molecular-level changes within corals and other
endosymbioses exposed to changes in their environment.
PMID- 22046303
TI - Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating
the immune response.
AB - Amniotic fluid stem (AFS) cells are broadly multipotent, can be expanded
extensively in culture, are not tumorigenic and can be readily cryopreserved for
cell banking. Mesenchymal stem cells (MSC) show immunomodulatory activity and
secrete a wide spectrum of cytokines and chemokines that suppress inflammatory
responses, block mixed lymphocyte reactions (MLR) and other immune reactions, and
have proven therapeutic against conditions such as graft-versus-host disease. AFS
cells resemble MSCs in many respects including surface marker expression and
differentiation potential. We therefore hypothesized that AFS cells may exhibit
similar immunomodulatory capabilities. We present data to demonstrate that direct
contact with AFS cells inhibits lymphocyte activation. In addition, we show that
cell-free supernatants derived from AFS cells primed with total blood monocytes
or IL-1beta, a cytokine released by monocytes and essential in mediation of the
inflammatory response, also inhibited lymphocyte activation. Further
investigation of AFS cell-free supernatants by protein array revealed secretion
of multiple factors in common with MSCs that are known to be involved in immune
regulation including growth related oncogene (GRO) and monocyte chemotactic
protein (MCP) family members as well as interleukin-6 (IL-6). AFS cells activated
by PBMCs released several additional cytokines as compared to BM-MSCs, including
macrophage inflammatory protein-3alpha (MIP-3alpha), MIP-1alpha and Activin. AFS
cells also released higher levels of MCP-1 and lower levels of MCP-2 compared to
BM-MSCs in response to IL-1beta activation. This suggests that there may be some
AFS-specific mechanisms of inhibition of lymphocyte activation. Our results
indicate that AFS cells are able to suppress inflammatory responses in vitro and
that soluble factors are an essential component in the communication between
lymphocytes and AFS cells. Their extensive self-renewal capacity, possibility for
banking and absence of tumorigenicity may make AFS cells a superior source of
stable, well characterized "off the shelf" immunomodulatory cells for a variety
of immunotherapies.
PMID- 22046304
TI - Homeostatic regulation of marginal zone B cells by invariant natural killer T
cells.
AB - Marginal zone B cells (MZB) mount a rapid antibody response, potently activate
naive T cells, and are enriched in autoreactive B cells. MZBs express high levels
of CD1d, the restriction element for invariant natural killer T cells (iNKT).
Here, we examined the effect of iNKT cells on MZB cell activation and numbers in
vitro and in vivo in normal and autoimmune mice. Results show that iNKT cells
activate MZBs, but restrict their numbers in vitro and in vivo in normal BALB/c
and C57/BL6 mice. iNKT cells do so by increasing the activation-induced cell
death and curtailing proliferation of MZB cells, whereas they promote the
proliferation of follicular B cells. Sorted iNKT cells can directly execute this
function, without help from other immune cells. Such MZB regulation by iNKTs is
mediated, at least in part, via CD1d on B cells in a contact-dependent manner,
whereas iNKT-induced proliferation of follicular B cells occurs in a contact- and
CD1d-independent manner. Finally, we show that iNKT cells reduce 'autoreactive'
MZB cells in an anti-DNA transgenic model, and limit MZB cell numbers in
autoimmune-prone (NZB*NZW)F1 and non-obese diabetic mice, suggesting a
potentially new mechanism whereby iNKT cells might regulate pathologic
autoimmunity. Differential regulation of follicular B cells versus potentially
autoreactive MZBs by iNKT cells has important implications for autoimmune
diseases as well as for conditions that require a rapid innate B cell response.
PMID- 22046305
TI - Peptide fingerprinting of Alzheimer's disease in cerebrospinal fluid:
identification and prospective evaluation of new synaptic biomarkers.
AB - BACKGROUND: Today, dementias are diagnosed late in the course of disease. Future
treatments have to start earlier in the disease process to avoid disability
requiring new diagnostic tools. The objective of this study is to develop a new
method for the differential diagnosis and identification of new biomarkers of
Alzheimer's disease (AD) using capillary-electrophoresis coupled to mass
spectrometry (CE-MS) and to assess the potential of early diagnosis of AD.
METHODS AND FINDINGS: Cerebrospinal fluid (CSF) of 159 out-patients of a memory
clinic at a University Hospital suffering from neurodegenerative disorders and 17
cognitively-healthy controls was used to create differential peptide pattern for
dementias and prospective blinded-comparison of sensitivity and specificity for
AD diagnosis against the Criterion standard in a naturalistic prospective sample
of patients. Sensitivity and specificity of the new method compared to standard
diagnostic procedures and identification of new putative biomarkers for AD was
the main outcome measure. CE-MS was used to reliably detect 1104 low-molecular
weight peptides in CSF. Training-sets of patients with clinically secured
sporadic Alzheimer's disease, frontotemporal dementia, and cognitively healthy
controls allowed establishing discriminative biomarker pattern for diagnosis of
AD. This pattern was already detectable in patients with mild cognitive
impairment (MCI). The AD-pattern was tested in a prospective sample of patients
(n = 100) and AD was diagnosed with a sensitivity of 87% and a specificity of
83%. Using CSF measurements of beta-amyloid1-42, total-tau, and phospho(181)-tau,
AD-diagnosis had a sensitivity of 88% and a specificity of 67% in the same
sample. Sequence analysis of the discriminating biomarkers identified fragments
of synaptic proteins like proSAAS, apolipoprotein J, neurosecretory protein VGF,
phospholemman, and chromogranin A. CONCLUSIONS: The method may allow early
differential diagnosis of various dementias using specific peptide fingerprints
and identification of incipient AD in patients suffering from MCI. Identified
biomarkers facilitate face validity for the use in AD diagnosis.
PMID- 22046306
TI - Expression of sympathetic nervous system genes in Lamprey suggests their
recruitment for specification of a new vertebrate feature.
AB - The sea lamprey is a basal, jawless vertebrate that possesses many neural crest
derivatives, but lacks jaws and sympathetic ganglia. This raises the possibility
that the factors involved in sympathetic neuron differentiation were either a
gnathostome innovation or already present in lamprey, but serving different
purposes. To distinguish between these possibilities, we isolated lamprey
homologues of transcription factors associated with peripheral ganglion formation
and examined their deployment in lamprey embryos. We further performed DiI
labeling of the neural tube combined with neuronal markers to test if neural
crest-derived cells migrate to and differentiate in sites colonized by
sympathetic ganglia in jawed vertebrates. Consistent with previous anatomical
data in adults, our results in lamprey embryos reveal that neural crest cells
fail to migrate ventrally to form sympathetic ganglia, though they do form dorsal
root ganglia adjacent to the neural tube. Interestingly, however, paralogs of the
battery of transcription factors that mediate sympathetic neuron differentiation
(dHand, Ascl1 and Phox2b) are present in the lamprey genome and expressed in
various sites in the embryo, but fail to overlap in any ganglionic structures.
This raises the intriguing possibility that they may have been recruited during
gnathostome evolution to a new function in a neural crest derivative.
PMID- 22046307
TI - Reversal of fragile X phenotypes by manipulation of AbetaPP/Abeta levels in
Fmr1KO mice.
AB - Fragile X syndrome (FXS) is the most common form of inherited intellectual
disability and the leading known genetic cause of autism. Fragile X mental
retardation protein (FMRP), which is absent or expressed at substantially reduced
levels in FXS, binds to and controls the postsynaptic translation of amyloid beta
protein precursor (AbetaPP) mRNA. Cleavage of AbetaPP can produce beta-amyloid
(Abeta), a 39-43 amino acid peptide mis-expressed in Alzheimer's disease (AD) and
Down syndrome (DS). Abeta is over-expressed in the brain of Fmr1(KO) mice,
suggesting a pathogenic role in FXS. To determine if genetic reduction of
AbetaPP/Abeta rescues characteristic FXS phenotypes, we assessed audiogenic
seizures (AGS), anxiety, the ratio of mature versus immature dendritic spines and
metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD) in
Fmr1(KO) mice after removal of one App allele. All of these phenotypes were
partially or completely reverted to normal. Plasma Abeta(1-42) was significantly
reduced in full-mutation FXS males compared to age-matched controls while
cortical and hippocampal levels were somewhat increased, suggesting that Abeta is
sequestered in the brain. Evolving therapies directed at reducing Abeta in AD may
be applicable to FXS and Abeta may serve as a plasma-based biomarker to
facilitate disease diagnosis or assess therapeutic efficacy.
PMID- 22046308
TI - A fresh insight into transmission of schistosomiasis: a misleading tale of
Biomphalaria in Lake Victoria.
AB - Lake Victoria is a known hot-spot for Schistosoma mansoni, which utilises
freshwater snails of the genus Biomphalaria as intermediate hosts. Different
species of Biomphalaria are associated with varying parasite compatibility,
affecting local transmission. It is thought that two species, B. choanomphala and
B. sudanica, inhabit Lake Victoria; despite their biomedical importance, the
taxonomy of these species has not been thoroughly examined. This study combined
analysis of morphological and molecular variables; the results demonstrated that
molecular groupings were not consistent with morphological divisions. Habitat
significantly predicted morphotype, suggesting that the different Lake Victorian
forms of Biomphalaria are ecophentoypes of one species. The nomenclature should
be revised accordingly; the names B. choanomphala choanomphala and B. c. sudanica
are proposed. From a public health perspective, these findings can be utilised by
policy-makers for better understanding of exposure risk, resulting in more
effective and efficient control initiatives.
PMID- 22046309
TI - Adverse events of interferon beta-1a: a prospective multi-centre international
ICH-GCP-based CRO-supported external validation study in daily practice.
AB - BACKGROUND: Due to methodological shortcomings the available post-registration
data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)
treated patients fail to adequately validate phase III data and only partially
inform on safety in daily practice. We assessed AEs in relapsing remitting
multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in
daily practice using data quality assurance measures similar to those in phase
III trials. METHODS: A prospective, International Conference on Harmonization
(ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)
supported study in 36 practices in the Netherlands, Belgium, the United Kingdom
and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS
patients were assessed for AEs' severity (mild, moderate, severe) and
relationship to treatment (not, unlikely, likely, definite). Data were compared
with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the
patients experienced one or more AEs that were likely or definitely related to
INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of
these were mild, and 3% severe. 6.6% of the patients discontinued treatment
because of an AE. Compared to the pivotal phase III trial, we found statistically
significantly lower incidences for most of the common AEs: headache, muscle ache,
fatigue, fever, chills, nausea. One patient died following two cerebral vascular
events in study month 22, both AEs were assessed as not related to INFb-1a.
CONCLUSION: Three out of four RRMS patients treated with IM INFb-1a in daily
practice experience treatment-related AEs, most of these being mild. Our data
externally validate the favorable phase III safety profile of IM INFb-1a and
suggest that the real-life incidence of treatment-related AEs is less than
reported in the pivotal phase III trial. Larger studies are needed to detect
rare, potentially hazardous AEs of IM INFb-1a.
PMID- 22046310
TI - Evidence for positive selection on the leptin gene in Cetacea and Pinnipedia.
AB - The leptin gene has received intensive attention and scientific investigation for
its importance in energy homeostasis and reproductive regulation in mammals.
Furthermore, study of the leptin gene is of crucial importance for public health,
particularly for its role in obesity, as well as for other numerous physiological
roles that it plays in mammals. In the present work, we report the identification
of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly
available leptin sequences from mammalian genome assemblies and previous studies.
Our study provides evidence for positive selection in the suborder Odontoceti
(toothed whales) of the Cetacea and the family Phocidae (earless seals) of the
Pinnipedia. We also detected positive selection in several leptin gene residues
in these two lineages. To test whether leptin and its receptor evolved in a
coordinated manner, we analyzed 24 leptin receptor gene (LPR) sequences from
available mammalian genome assemblies and other published data. Unlike the case
of leptin, our analyses did not find evidence of positive selection for LPR
across the Cetacea and Pinnipedia lineages. In line with this, positively
selected sites identified in the leptin genes of these two lineages were located
outside of leptin receptor binding sites, which at least partially explains why
co-evolution of leptin and its receptor was not observed in the present study.
Our study provides interesting insights into current understanding of the
evolution of mammalian leptin genes in response to selective pressures from life
in an aquatic environment, and leads to a hypothesis that new tissue specificity
or novel physiologic functions of leptin genes may have arisen in both
odontocetes and phocids. Additional data from other species encompassing varying
life histories and functional tests of the adaptive role of the amino acid
changes identified in this study will help determine the factors that promote the
adaptive evolution of the leptin genes in marine mammals.
PMID- 22046311
TI - Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal
infections.
AB - Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released
after the fusion of multivesicular bodies (MVBs) with the plasma membrane. While
initial studies suggested that the role of exosomes was limited to the removal of
proteins during the maturation of reticulocytes to erythrocytes, recent studies
indicate that they are produced by different types of cells and are involved in
promoting inter-cellular communication and antigen presentation. Here, we
describe the isolation and characterization of exosomes from peripheral blood of
BALB/c mice infected with the reticulocyte-prone non-lethal Plasmodium yoelii 17X
strain. Importantly, proteomic analysis revealed the presence of parasite
proteins in these vesicles. Moreover, immunization of mice with purified exosomes
elicited IgG antibodies capable of recognizing P. yoelii-infected red blood
cells. Furthermore, lethal challenge of immunized mice with the normocyte-prone
lethal P. yoelii 17XL strain caused a significant attenuation in the course of
parasitaemia, increased survival time, and altered the cell tropism to
reticulocytes. These results were obtained also when the exosomes were isolated
from a P. yoelii-infected reticulocyte culture indicating that reticulocyte
derived exosomes carry antigens and are involved in immune modulation. Moreover,
inclusion of CpG ODN 1826 in exosome immunizations elicited IgG2a and IgG2b
antibodies and promoted survival, clearance of parasites and subsequent sterile
protection of 83% of the animals challenged with P. yoelli 17XL. To our
knowledge, this is the first report of immune responses elicited by exosomes
derived from reticulocytes opening new avenues for the modulation of anti-malaria
responses.
PMID- 22046312
TI - Efficient generation of fully reprogrammed human iPS cells via polycistronic
retroviral vector and a new cocktail of chemical compounds.
AB - Direct reprogramming of human somatic cells into induced pluripotent stem (iPS)
cells by defined transcription factors (TFs) provides great potential for
regenerative medicine and biomedical research. This procedure has many
challenges, including low reprogramming efficiency, many partially reprogrammed
colonies, somatic coding mutations in the genome, etc. Here, we describe a simple
approach for generating fully reprogrammed human iPS cells by using a single
polycistronic retroviral vector expressing four human TFs in a single open
reading frame (ORF), combined with a cocktail containing three small molecules
(Sodium butyrate, SB431542, and PD0325901). Our results demonstrate that human
iPS cells generated by this approach express human ES cells markers and exhibit
pluripotency demonstrated by their abilities to differentiate into the three germ
layers in vitro and in vivo. Notably, this approach not only provides a much
faster reprogramming process but also significantly diminishes partially
reprogrammed iPS cell colonies, thus facilitating efficient isolation of desired
fully reprogrammed iPS cell colonies.
PMID- 22046313
TI - Social and nonsocial content differentially modulates visual attention and
autonomic arousal in Rhesus macaques.
AB - The sophisticated analysis of gestures and vocalizations, including assessment of
their emotional valence, helps group-living primates efficiently navigate their
social environment. Deficits in social information processing and emotion
regulation are important components of many human psychiatric illnesses, such as
autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of
social information processing and emotion regulation requires a multidisciplinary
approach that benefits from comparative studies of humans and animal models.
However, many questions remain regarding the relationship between visual
attention and arousal while processing social stimuli. Using noninvasive infrared
eye-tracking methods, we measured the visual social attention and physiological
arousal (pupil diameter) of adult male rhesus monkeys (Macaca mulatta) as they
watched social and nonsocial videos. We found that social videos, as compared to
nonsocial videos, captured more visual attention, especially if the social
signals depicted in the videos were directed towards the subject. Subject
directed social cues and nonsocial nature documentary footage, compared to videos
showing conspecifics engaging in naturalistic social interactions, generated
larger pupil diameters (indicating heightened sympathetic arousal). These
findings indicate that rhesus monkeys will actively engage in watching videos of
various kinds. Moreover, infrared eye tracking technology provides a mechanism
for sensitively gauging the social interest of presented stimuli. Adult male
rhesus monkeys' visual attention and physiological arousal do not always trend in
the same direction, and are likely influenced by the content and novelty of a
particular visual stimulus. This experiment creates a strong foundation for
future experiments that will examine the neural network responsible for social
information processing in nonhuman primates. Such studies may provide valuable
information relevant to interpreting the neural deficits underlying human
psychiatric illnesses such as autism, schizophrenia and social anxiety disorder.
PMID- 22046314
TI - Pyomelanin formation in Aspergillus fumigatus requires HmgX and the
transcriptional activator HmgR but is dispensable for virulence.
AB - The opportunistic human pathogenic fungus Aspergillus fumigatus is able to
produce the dark brown pigment pyomelanin by degradation of L-tyrosine.
Pyomelanin was shown to protect the fungus against reactive oxygen intermediates
as well as cell wall disturbing compounds and is therefore assumed to protect
against immune effector cells during the infection process. Several genes for
tyrosine degradation and pyomelanin formation are organized in a cluster in the
genome of A. fumigatus. Here, we aimed at further analyzing tyrosine degradation
and a possible role of pyomelanin in virulence. For this purpose, the function of
two not yet characterized genes of the cluster, i.e., hmgX and hmgR, was
analyzed. Generation of corresponding gene deletion mutants and reconstituted
strains revealed that hmgX and hmgR are essential for tyrosine degradation. Both
mutants, DeltahmgX and DeltahmgR, were not able to use tyrosine as sole carbon or
nitrogen source and revealed impaired pyomelanin production. HmgR harbors a
Zn(II)2Cys6-DNA binding domain. Analyses of the steady state mRNA levels revealed
that HmgR acts as a transcriptional activator for the genes of the tyrosine
degradation cluster. Consistently, an HmgR-eGFP fusion protein was localized in
the nucleus of A. fumigatus cells. By contrast, HmgX was found to be localized in
the cytoplasm and does not contribute to regulation of gene transcription. HPLC
analyses showed that HmgX is crucial for the conversion of p
hydroxyphenylpyruvate to homogentisic acid, the main intermediate in pyomelanin
formation. Thus, HmgX is supposed to function as an accessory factor to mediate
specific activity of HppD. Remarkably, the ability to degrade tyrosine and to
form pyomelanin is dispensable for virulence of A. fumigatus in a murine
infection model.
PMID- 22046315
TI - Parallel evolution of KCNQ4 in echolocating bats.
AB - High-frequency hearing is required for echolocating bats to locate, range and
identify objects, yet little is known about its molecular basis. The discovery of
a high-frequency hearing-related gene, KCNQ4, provides an opportunity to address
this question. Here, we obtain the coding regions of KCNQ4 from 15 species of
bats, including echolocating bats that have higher frequency hearing and non
echolocating bats that have the same ability as most other species of mammals.
The strongly supported protein-tree resolves a monophyletic group containing all
bats with higher frequency hearing and this arrangement conflicts with the
phylogeny of bats in which these species are paraphyletic. We identify five
parallel evolved sites in echolocating bats belonging to both suborders. The
evolutionary trajectories of the parallel sites suggest the independent gain of
higher frequency hearing ability in echolocating bats. This study highlights the
usefulness of convergent or parallel evolutionary studies for finding phenotype
related genes and contributing to the resolution of evolutionary problems.
PMID- 22046316
TI - Genetic variation of the IL-28B promoter affecting gene expression.
AB - The current standard of care for the treatment of chronic hepatitis C is
pegylated interferon-alpha (PEG-IFNalpha) and ribavirin (RBV). The treatment
achieves a sustained viral clearance in only approximately 50% of patients.
Recent whole genome association studies revealed that single nucleotide
polymorphisms (SNPs) around IL-28B have been associated with response to the
standard therapy and could predict treatment responses at approximately 80%.
However, it is not clear which SNP is most informative because the genomic region
containing significant SNPs shows strong linkage disequilibrium. We focused on
SNPs in close proximity to the IL-28B gene to evaluate the function of each and
identify the SNP affecting the IL-28B expression level most. The structures of IL
28A/B from 5' to 3'-UTR were determined by complete cDNA cloning. Both IL-28A and
28B genes consisted of 6 exons, differing from the CCDS data of NCBI. Two intron
SNPs and a nonsynonymous SNP did not affect IL-28B gene function and expression
levels but a SNP located in the proximal promoter region influenced gene
expression. A (TA) dinucleotide repeat, rs72258881, located in the promoter
region was discovered by our functional studies of the proximal SNPs upstream of
IL-28B; the transcriptional activity of the promoter increased gradually in a
(TA)(n) length-dependent manner following IFN-alpha and lipopolysaccharide
stimulation. Healthy Japanese donors exhibited a broad range of (TA) dinucleotide
repeat numbers from 10 to 18 and the most prevalent genotype was 12/12 (75%),
differing from the database (13/13). However, genetic variation of IL-28A
corresponding to that of IL-28B was not detected in these Japanese donors. These
findings suggest that the dinucleotide repeat could be associated with the
transcriptional activity of IL-28B as well as being a marker to improve the
prediction of the response to interferon-based hepatitis C virus treatment.
PMID- 22046317
TI - Control of bone resorption by semaphorin 4D is dependent on ovarian function.
AB - Osteoporosis is one of the most common bone pathologies, which are characterized
by a decrease in bone mass. It is well established that bone mass, which results
from a balanced bone formation and bone resorption, is regulated by many
hormonal, environmental and genetic factors. Here we report that the immune
semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D
deficient primary osteoclasts showed impaired spreading, adhesion, migration and
resorption due to altered beta3 integrin sub-unit downstream signaling. In
apparent accordance with these in vitro results, Sema4D deletion in sexually
mature female mice led to a high bone mass phenotype due to defective bone
resorption by osteoclasts. Mutant males, however, displayed normal bone mass and
the female osteopetrotic phenotype was only detected at the onset of sexual
maturity, indicating that, in vivo, this intrinsic osteoclast defect might be
overcome in these mice. Using bone marrow cross transplantation, we confirmed
that Sema4D controls bone resorption through an indirect mechanism. In addition,
we show that Sema4D -/- mice were less fertile than their WT littermates. A
decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian
follicles can explain this attenuated fertility. Interestingly, ovariectomy
abrogated the bone resorption phenotype in Sema4D -/- mice, providing the
evidence that the observed high bone mass phenotype is strictly dependent on
ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an
indirect regulator of bone resorption, which acts via its effect on reproductive
function.
PMID- 22046318
TI - Quantitative proteomics reveals cellular targets of celastrol.
AB - Celastrol, a natural substance isolated from plant extracts used in traditional
Chinese medicine, has been extensively investigated as a possible drug for
treatment of cancer, autoimmune diseases, and protein misfolding disorders.
Although studies focusing on celastrol's effects in specific cellular pathways
have revealed a considerable number of targets in a diverse array of in vitro
models there is an essential need for investigations that can provide a global
view of its effects. To assess cellular effects of celastrol and to identify
target proteins as biomarkers for monitoring treatment regimes, we performed
large-scale quantitative proteomics in cultured human lymphoblastoid cells, a
cell type that can be readily prepared from human blood samples. Celastrol
substantially modified the proteome composition and 158 of the close to 1800
proteins with robust quantitation showed at least a 1.5 fold change in protein
levels. Up-regulated proteins play key roles in cytoprotection with a prominent
group involved in quality control and processing of proteins traversing the
endoplasmic reticulum. Increased levels of proteins essential for the cellular
protection against oxidative stress including heme oxygenase 1, several
peroxiredoxins and thioredoxins as well as proteins involved in the control of
iron homeostasis were also observed. Specific analysis of the mitochondrial
proteome strongly indicated that the mitochondrial association of certain
antioxidant defense and apoptosis-regulating proteins increased in cells exposed
to celastrol. Analysis of selected mRNA transcripts showed that celastrol
activated several different stress response pathways and dose response studies
furthermore showed that continuous exposure to sub-micromolar concentrations of
celastrol is associated with reduced cellular viability and proliferation. The
extensive catalog of regulated proteins presented here identifies numerous
cellular effects of celastrol and constitutes a valuable biomarker tool for the
development and monitoration of disease treatment strategies.
PMID- 22046319
TI - Differential palmit(e)oylation of Wnt1 on C93 and S224 residues has overlapping
and distinct consequences.
AB - Though the mechanisms by which cytosolic/intracellular proteins are regulated by
the post-translational addition of palmitate adducts is well understood, little
is known about how this lipid modification affects secreted ligands, such as
Wnts. Here we use mutational analysis to show that differential modification of
the two known palmit(e)oylated residues of Wnt1, C93 and S224, has both
overlapping and distinct consequences. Though the relative roles of each residue
are similar with respect to stability and secretion, two distinct biological
assays in L cells show that modification of C93 primarily modulates signaling via
a beta-catenin independent pathway while S224 is crucial for beta-catenin
dependent signaling. In addition, pharmacological inhibition of Porcupine
(Porcn), an upstream regulator of Wnt, by IWP1, specifically inhibited beta
catenin dependent signaling. Consistent with these observations, mapping of amino
acids in peptide domains containing C93 and S224 demonstrate that acylation of
C93 is likely to be Porcn-independent while that of S224 is Porcn-dependent.
Cumulatively, our data strongly suggest that C93 and S224 are modified by
distinct enzymes and that the differential modification of these sites has the
potential to influence Wnt signaling pathway choice.
PMID- 22046320
TI - An alignment-free approach for eukaryotic ITS2 annotation and phylogenetic
inference.
AB - The ITS2 gene class shows a high sequence divergence among its members that have
complicated its annotation and its use for reconstructing phylogenies at a higher
taxonomical level (beyond species and genus). Several alignment strategies have
been implemented to improve the ITS2 annotation quality and its use for
phylogenetic inferences. Although, alignment based methods have been exploited to
the top of its complexity to tackle both issues, no alignment-free approaches
have been able to successfully address both topics. By contrast, the use of
simple alignment-free classifiers, like the topological indices (TIs) containing
information about the sequence and structure of ITS2, may reveal to be a useful
approach for the gene prediction and for assessing the phylogenetic relationships
of the ITS2 class in eukaryotes. Thus, we used the TI2BioP (Topological Indices
to BioPolymers) methodology [1], [2], freely available at
http://ti2biop.sourceforge.net/ to calculate two different TIs. One class was
derived from the ITS2 artificial 2D structures generated from DNA strings and the
other from the secondary structure inferred from RNA folding algorithms. Two
alignment-free models based on Artificial Neural Networks were developed for the
ITS2 class prediction using the two classes of TIs referred above. Both models
showed similar performances on the training and the test sets reaching values
above 95% in the overall classification. Due to the importance of the ITS2 region
for fungi identification, a novel ITS2 genomic sequence was isolated from
Petrakia sp. This sequence and the test set were used to comparatively evaluate
the conventional classification models based on multiple sequence alignments like
Hidden Markov based approaches, revealing the success of our models to identify
novel ITS2 members. The isolated sequence was assessed using traditional and
alignment-free based techniques applied to phylogenetic inference to complement
the taxonomy of the Petrakia sp. fungal isolate.
PMID- 22046321
TI - Improved adsorption of an Enterococcus faecalis bacteriophage PhiEF24C with a
spontaneous point mutation.
AB - Some bacterial strains of the multidrug-resistant Gram-positive bacteria
Enterococcus faecalis can significantly reduce the efficacy of conventional
antimicrobial chemotherapy. Thus, the introduction of bacteriophage (phage)
therapy is expected, where a phage is used as a bioagent to destroy bacteria. E.
faecalis phage PhiEF24C is known to be a good candidate for a therapeutic phage
against E. faecalis. However, this therapeutic phage still produces nonuniform
antimicrobial effects with different bacterial strains of the same species and
this might prove detrimental to its therapeutic effects. One solution to this
problem is the preparation of mutant phages with higher activity, based on a
scientific rationale. This study isolated and analyzed a spontaneous mutant
phage, PhiEF24C-P2, which exhibited higher infectivity against various bacterial
strains when compared with phage PhiEF24C. First, the improved bactericidal
effects of phage PhiEF24C-P2 were attributable to its increased adsorption rate.
Moreover, genomic sequence scanning revealed that phage PhiEF24C-P2 had a point
mutation in orf31. Proteomic analysis showed that ORF31 (mw, 203 kDa) was present
in structural components, and immunological analysis using rabbit-derived
antibodies showed that it was a component of a long, flexible fine tail fiber
extending from the tail end. Finally, phage PhiEF24C-P2 also showed higher
bactericidal activity in human blood compared with phage PhiEF24C using the in
vitro assay system. In conclusion, the therapeutic effects of phage PhiEF24C-P2
were improved by a point mutation in gene orf31, which encoded a tail fiber
component.
PMID- 22046322
TI - Protective effects of white button mushroom (Agaricus bisporus) against hepatic
steatosis in ovariectomized mice as a model of postmenopausal women.
AB - Nonalcoholic fatty liver disease (NAFLD) includes various hepatic pathologies
ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis
and cirrhosis. Estrogen provides a protective effect on the development of NAFLD
in women. Therefore, postmenopausal women have a higher risk of developing NAFLD.
Hepatic steatosis is an early stage of fatty liver disease. Steatosis can develop
to the aggressive stages (nonalcoholic steatohepatitis, fibrosis and cirrhosis).
Currently, there is no specific drug to prevent/treat these liver diseases. In
this study, we found that white button mushroom (WBM), Agaricus Bisporus, has
protective effects against liver steatosis in ovariectomized (OVX) mice (a model
of postmenopausal women). OVX mice were fed a high fat diet supplemented with WBM
powder. We found that dietary WBM intake significantly lowered liver weight and
hepatic injury markers in OVX mice. Pathological examination of liver tissue
showed less fat accumulation in the livers of mice on WBM diet; moreover, these
animals had improved glucose clearance ability. Microarray analysis revealed that
genes related to the fatty acid biosynthesis pathway, particularly the genes for
fatty acid synthetase (Fas) and fatty acid elongase 6 (Elovl6), were down
regulated in the liver of mushroom-fed mice. In vitro mechanistic studies using
the HepG2 cell line showed that down-regulation of the expression of FAS and
ELOVL6 by WBM extract was through inhibition of Liver X receptor (LXR) signaling
and its downstream transcriptional factor SREBP1c. These results suggest that WBM
is protective against hepatic steatosis and NAFLD in OVX mice as a model for
postmenopausal women.
PMID- 22046323
TI - Paromomycin affects translation and vesicle-mediated trafficking as revealed by
proteomics of paromomycin -susceptible -resistant Leishmania donovani.
AB - Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis
(VL) and is responsible for significant mortality and morbidity. Increasing
resistance towards antimonial drugs poses a great challenge in chemotherapy of
VL. Paromomycin is an aminoglycosidic antibiotic and is one of the drugs
currently being used in the chemotherapy of cutaneous and visceral leishmaniasis.
To understand the mode of action of this antibiotic at the molecular level, we
have investigated the global proteome differences between the wild type AG83
strain and a paromomycin resistant (PRr) strain of L. donovani. Stable isotope
labeling of amino acids in cell culture (SILAC) followed by quantitative mass
spectrometry of the wild type AG83 strain and the paromomycin resistant (PRr)
strain identified a total of 226 proteins at >= 95% confidence. Data analysis
revealed upregulation of 29 proteins and down-regulation of 21 proteins in the
PRr strain. Comparative proteomic analysis of the wild type and the paromomycin
resistant strains showed upregulation of the ribosomal proteins in the resistant
strain indicating role in translation. Elevated levels of glycolytic enzymes and
stress proteins were also observed in the PRr strain. Most importantly, we
observed upregulation of proteins that may have a role in intracellular survival
and vesicular trafficking in the PRr strain. Furthermore, ultra-structural
analysis by electron microscopy demonstrated increased number of vesicular
vacuoles in PRr strain when compared to the wild-type strain. Drug affinity pull
down assay followed by mass spectrometery identified proteins in L. donovani wild
type strain that were specifically and covalently bound to paromomycin. These
results provide the first comprehensive insight into the mode of action and
underlying mechanism of resistance to paromomycin in Leishmania donovani.
PMID- 22046324
TI - Characterization of protection afforded by a bivalent virus-like particle vaccine
against bluetongue virus serotypes 1 and 4 in sheep.
AB - BACKGROUND: Bluetongue virus (BTV) is an economically important, arthropod borne,
emerging pathogen in Europe, causing disease mainly in sheep and cattle. Routine
vaccination for bluetongue would require the ability to distinguish between
vaccinated and infected individuals (DIVA). Current vaccines are effective but
are not DIVA. Virus-like particles (VLPs) are highly immunogenic structural
mimics of virus particles, that only contain a subset of the proteins present in
a natural infection. VLPs therefore offer the potential for the development of
DIVA compatible bluetongue vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Merino sheep
were vaccinated with either monovalent BTV-1 VLPs or a bivalent mixture of BTV-1
VLPs and BTV-4 VLPs, and challenged with virulent BTV-1 or BTV-4. Animals were
monitored for clinical signs, antibody responses, and viral RNA. 19/20 animals
vaccinated with BTV-1 VLPs either alone or in combination with BTV-4 VLPs
developed neutralizing antibodies to BTV-1, and group specific antibodies to BTV
VP7. The one animal that showed no detectable neutralizing antibodies, or group
specific antibodies, had detectable viral RNA following challenge but did not
display any clinical signs on challenge with virulent BTV-1. In contrast, all
control animals' demonstrated classical clinical signs for bluetongue on
challenge with the same virus. Six animals were vaccinated with bivalent vaccine
and challenged with virulent BTV-4, two of these animals had detectable viral
levels of viral RNA, and one of these showed clinical signs consistent with BTV
infection and died. CONCLUSIONS: There is good evidence that BTV-1 VLPs delivered
as monovalent or bivalent immunogen protect from bluetongue disease on challenge
with virulent BTV-1. However, it is possible that there is some interference in
protective response for BTV-4 in the bivalent BTV-1 and BTV-4 VLP vaccine. This
raises the question of whether all combinations of bivalent BTV vaccines are
possible, or if immunodominance of particular serotypes could interfere with
vaccine efficacy.
PMID- 22046325
TI - A short-term physical activity randomized trial in the Lower Mississippi Delta.
AB - BACKGROUND: The purpose of this study was to determine if a short-term pedometer
based intervention results in immediate increases in time spent in moderate-to
vigorous physical activity (MVPA) compared to a minimal educational intervention.
METHODS: A sample of 43 overweight adults 35 to 64 years of age participated in a
one week pedometer-based feasibility trial monitored by accelerometry.
Participants were randomized into a one-week education-only group or a group that
also wore a pedometer. Accelerometer-measured MVPA was measured over 7 days at
baseline and again for 7 days immediately post-intervention. RESULTS: Minutes of
MVPA increased significantly in the overall sample (p = 0.02); however, the
effect of adding the pedometer to the education program was not significant (p =
0.89). Mean (+/-SE) MVPA increased from 12.7 +/- 2.4 min/day to 16.2 +/- 3.6
min/day in the education-only group and from 13.2 +/- 3.3 min/day to 16.3 +/- 3.9
min/day in the education+pedometer group. The correlation between change in
steps/day and change in MVPA was 0.69 (p<0.0001). CONCLUSIONS: The results of
this study suggest that the addition of a pedometer to a short-term education
program does not produce added benefits with respect to increasing physical
activity in the Lower Mississippi Delta. TRIAL REGISTRATION: ClinicalTrials.gov
NCT01264757.
PMID- 22046326
TI - 'Smoking genes': a genetic association study.
AB - Some controversy exists on the specific genetic variants that are associated with
nicotine dependence and smoking-related phenotypes. The purpose of this study was
to analyse the association of smoking status and smoking-related phenotypes
(included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1*2,
CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (-48T>G) [rs28399433], CYP2A6*12,
CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A),
CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3
546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2
ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1
118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms
in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never
smokers (controls, N = 80). The results showed significant between-group
differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of
variant alleles, the odds ratio (OR) for being a non-smoker in individuals with
the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms
was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared
with the wild-type genotype, the OR for being a non-smoker in carriers of the
minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant
genotype effect (all P<=0.017) for the following smoking-related phenotypes: (i)
cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2,
CYP2A6*1*2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine
dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results
suggest that genetic variants potentially involved in nicotine metabolization
(mainly, CYP2A6 polymorphisms) are those showing the strongest association with
smoking-related phenotypes, as opposed to genetic variants influencing the brain
effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5),
serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).
PMID- 22046327
TI - Size-specific tree mortality varies with neighbourhood crowding and disturbance
in a Montane Nothofagus forest.
AB - Tree mortality is a fundamental process governing forest dynamics, but
understanding tree mortality patterns is challenging because large, long-term
datasets are required. Describing size-specific mortality patterns can be
especially difficult, due to few trees in larger size classes. We used permanent
plot data from Nothofagus solandri var. cliffortioides (mountain beech) forest on
the eastern slopes of the Southern Alps, New Zealand, where the fates of trees on
250 plots of 0.04 ha were followed, to examine: (1) patterns of size-specific
mortality over three consecutive periods spanning 30 years, each characterised by
different disturbance, and (2) the strength and direction of neighbourhood
crowding effects on size-specific mortality rates. We found that the size
specific mortality function was U-shaped over the 30-year period as well as
within two shorter periods characterised by small-scale pinhole beetle and
windthrow disturbance. During a third period, characterised by earthquake
disturbance, tree mortality was less size dependent. Small trees (<20 cm in
diameter) were more likely to die, in all three periods, if surrounded by a high
basal area of larger neighbours, suggesting that size-asymmetric competition for
light was a major cause of mortality. In contrast, large trees (>= 20 cm in
diameter) were more likely to die in the first period if they had few neighbours,
indicating that positive crowding effects were sometimes important for survival
of large trees. Overall our results suggest that temporal variability in size
specific mortality patterns, and positive interactions between large trees, may
sometimes need to be incorporated into models of forest dynamics.
PMID- 22046328
TI - Increased lipolysis and energy expenditure in a mouse model with severely
impaired glucagon secretion.
AB - BACKGROUND: Secretion of insulin and glucagon is triggered by elevated
intracellular calcium levels. Although the precise mechanism by which the calcium
signal is coupled to insulin and glucagon granule exocytosis is unclear,
synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent
insulin and glucagon secretion, and may function as a calcium sensor for insulin
and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired
glucose-stimulated insulin secretion and nearly abolished Ca(2+)-dependent
glucagon secretion in mice. Under non-stressed resting state, however,
synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced
glucagon level. METHODOLOGY/PRINCIPAL FINDINGS: We studied energy expenditure and
metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and
biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body
fat content, and exhibited higher oxygen consumption and basal metabolic rate.
Respiratory exchange ratio (RER) was lower in synaptotagmin-7 KO mice, suggesting
an increased use of lipid in their energy production. Consistent with lower RER,
gene expression profiles suggest enhanced lipolysis and increased capacity for
fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore,
expression of uncoupling protein 3 (UCP3) in skeletal muscle was approximately
doubled in the KO mice compared with control mice. CONCLUSIONS: These results
show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to
increased lipolysis and energy expenditure, and suggest that reduced glucagon
level may have broad influence on the overall metabolism in the mouse model.
PMID- 22046329
TI - The role of geomagnetic cues in green turtle open sea navigation.
AB - BACKGROUND: Laboratory and field experiments have provided evidence that sea
turtles use geomagnetic cues to navigate in the open sea. For instance, green
turtles (Chelonia mydas) displaced 100 km away from their nesting site were
impaired in returning home when carrying a strong magnet glued on the head.
However, the actual role of geomagnetic cues remains unclear, since magnetically
treated green turtles can perform large scale (>2000 km) post-nesting migrations
no differently from controls. METHODOLOGY/PRINCIPAL FINDINGS: In the present
homing experiment, 24 green turtles were displaced 200 km away from their nesting
site on an oceanic island, and tracked, for the first time in this type of
experiment, with Global Positioning System (GPS), which is able to provide much
more frequent and accurate locations than previously used tracking methods. Eight
turtles were magnetically treated for 24-48 h on the nesting beach prior to
displacement, and another eight turtles had a magnet glued on the head at the
release site. The last eight turtles were used as controls. Detailed analyses of
water masses-related (i.e., current-corrected) homing paths showed that
magnetically treated turtles were able to navigate toward their nesting site as
efficiently as controls, but those carrying magnets were significantly impaired
once they arrived within 50 km of home. CONCLUSIONS/SIGNIFICANCE: While green
turtles do not seem to need geomagnetic cues to navigate far from the goal, these
cues become necessary when turtles get closer to home. As the very last part of
the homing trip (within a few kilometers of home) likely depends on non-magnetic
cues, our results suggest that magnetic cues play a key role in sea turtle
navigation at an intermediate scale by bridging the gap between large and small
scale navigational processes, which both appear to depend on non-magnetic cues.
PMID- 22046330
TI - Dab1 (Disable homolog-1) reelin adaptor protein is overexpressed in the olfactory
bulb at early postnatal stages.
AB - Dab1 mediates reelin signalling and plays critical roles in early brain
development such as the stereotypical positioning of neurons in the brain. The
olfactory bulb undergoes a prominent layering reorganization, but shows not
apparent differences between wild type and reeler in the layer organization.
Therefore, an accurate regional and cellular simultaneous analysis of these
molecules becomes essential to clarify the role played by Dab1 upon Reelin
effect. The present study reveals a strong and consistent Dab1 mRNA and protein
expressions, throughout the olfactory bulb layers in both wild type and reeler
mice. In addition, noteworthy is the pattern of Dab1 location within cell nuclei
in both strains. Furthermore, a temporal increment of Dab1 expression levels is
detected from P0 to P15 in both strains, being the protein quantity higher in
reeler than in wild type mice. Altogether, our results revealed that Reln acts
directly from projection neurons via the production of different Reln fragments.
Changes in the pattern of Dab1 expression could reflect an alternative Reln
function in postnatal and adult stages, besides a possible regulation of Dab1 by
other molecules distinct to Reln.
PMID- 22046331
TI - Sialome of a generalist lepidopteran herbivore: identification of transcripts and
proteins from Helicoverpa armigera labial salivary glands.
AB - Although the importance of insect saliva in insect-host plant interactions has
been acknowledged, there is very limited information on the nature and complexity
of the salivary proteome in lepidopteran herbivores. We inspected the labial
salivary transcriptome and proteome of Helicoverpa armigera, an important
polyphagous pest species. To identify the majority of the salivary proteins we
have randomly sequenced 19,389 expressed sequence tags (ESTs) from a normalized
cDNA library of salivary glands. In parallel, a non-cytosolic enriched protein
fraction was obtained from labial salivary glands and subjected to two
dimensional gel electrophoresis (2-DE) and de novo peptide sequencing. This
procedure allowed comparison of peptides and EST sequences and enabled us to
identify 65 protein spots from the secreted labial saliva 2DE proteome. The mass
spectrometry analysis revealed ecdysone, glucose oxidase, fructosidase,
carboxyl/cholinesterase and an uncharacterized protein previously detected in H.
armigera midgut proteome. Consistently, their corresponding transcripts are among
the most abundant in our cDNA library. We did find redundancy of sequence
identification of saliva-secreted proteins suggesting multiple isoforms. As
expected, we found several enzymes responsible for digestion and plant offense.
In addition, we identified non-digestive proteins such as an arginine kinase and
abundant proteins of unknown function. This identification of secreted salivary
gland proteins allows a more comprehensive understanding of insect feeding and
poses new challenges for the elucidation of protein function.
PMID- 22046332
TI - High-throughput assay for the identification of compounds regulating osteogenic
differentiation of human mesenchymal stromal cells.
AB - Human mesenchymal stromal cells are regarded as the golden standard for cell
based therapies. They present multilineage differentiation potential and trophic
and immunosuppressive abilities, making them the best candidate for clinical
applications. Several molecules have been described to increase bone formation
and were mainly discovered by candidate approaches towards known signaling
pathways controlling osteogenesis. However, their bone forming potential is still
limited, making the search for novel molecules a necessity. High-throughput
screening (HTS) not only allows the screening of a large number of diverse
chemical compounds, but also allows the discovery of unexpected signaling
pathways and molecular mechanisms for a certain application, even without the
prior knowledge of the full molecular pathway. Typically HTS is performed in cell
lines, however, in this manuscript we have performed a phenotypical screen on
more clinically relevant human mesenchymal stromal cells, as a proof of principle
that HTS can be performed in those cells and can be used to find small molecules
that impact stem cell fate. From a library of pharmacologically active small
molecules, we were able to identify novel compounds with increased osteogenic
activity. These compounds allowed achieving levels of bone-specific alkaline
phosphatase higher than any other combination previously known. By combining
biochemical techniques, we were able to demonstrate that a medium to high
throughput phenotypic assay can be performed in academic research laboratories
allowing the discovery of novel molecules able to enhance stem cell
differentiation.
PMID- 22046333
TI - Development by design: mitigating wind development's impacts on wildlife in
Kansas.
AB - Wind energy, if improperly sited, can impact wildlife through direct mortality
and habitat loss and fragmentation, in contrast to its environmental benefits in
the areas of greenhouse gas, air quality, and water quality. Fortunately, risks
to wildlife from wind energy may be alleviated through proper siting and
mitigation offsets. Here we identify areas in Kansas where wind development is
incompatible with conservation, areas where wind development may proceed but with
compensatory mitigation for impacts, and areas where development could proceed
without the need for compensatory mitigation. We demonstrate that approximately
10.3 million ha in Kansas (48 percent of the state) has the potential to provide
478 GW of installed capacity while still meeting conservation goals. Of this
total, approximately 2.7 million ha would require no compensatory mitigation and
could produce up to 125 GW of installed capacity. This is 1,648 percent higher
than the level of wind development needed in Kansas by 2030 if the United States
is to get 20 percent of its electricity from wind. Projects that avoid and offset
impacts consistent with this analysis could be awarded "Green Certification."
Certification may help to expand and sustain the wind industry by facilitating
the completion of individual projects sited to avoid sensitive areas and
protecting the industry's reputation as an ecologically friendly source of
electricity.
PMID- 22046334
TI - Individual differences in impulsivity predict anticipatory eye movements.
AB - Impulsivity is the tendency to act without forethought. It is a personality trait
commonly used in the diagnosis of many psychiatric diseases. In clinical
practice, impulsivity is estimated using written questionnaires. However, answers
to questions might be subject to personal biases and misinterpretations. In order
to alleviate this problem, eye movements could be used to study differences in
decision processes related to impulsivity. Therefore, we investigated
correlations between impulsivity scores obtained with a questionnaire in healthy
subjects and characteristics of their anticipatory eye movements in a simple
smooth pursuit task. Healthy subjects were asked to answer the UPPS questionnaire
(Urgency Premeditation Perseverance and Sensation seeking Impulsive Behavior
scale), which distinguishes four independent dimensions of impulsivity: Urgency,
lack of Premeditation, lack of Perseverance, and Sensation seeking. The same
subjects took part in an oculomotor task that consisted of pursuing a target that
moved in a predictable direction. This task reliably evoked anticipatory saccades
and smooth eye movements. We found that eye movement characteristics such as
latency and velocity were significantly correlated with UPPS scores. The specific
correlations between distinct UPPS factors and oculomotor anticipation parameters
support the validity of the UPPS construct and corroborate neurobiological
explanations for impulsivity. We suggest that the oculomotor approach of
impulsivity put forth in the present study could help bridge the gap between
psychiatry and physiology.
PMID- 22046335
TI - Tracking traders' understanding of the market using e-communication data.
AB - Tracking the volume of keywords in Internet searches, message boards, or Tweets
has provided an alternative for following or predicting associations between
popular interest or disease incidences. Here, we extend that research by
examining the role of e-communications among day traders and their collective
understanding of the market. Our study introduces a general method that focuses
on bundles of words that behave differently from daily communication routines,
and uses original data covering the content of instant messages among all day
traders at a trading firm over a 40-month period. Analyses show that two word
bundles convey traders' understanding of same day market events and potential
next day market events. We find that when market volatility is high, traders'
communications are dominated by same day events, and when volatility is low,
communications are dominated by next day events. We show that the stronger the
traders' attention to either same day or next day events, the higher their
collective trading performance. We conclude that e-communication among traders is
a product of mass collaboration over diverse viewpoints that embodies unique
information about their weak or strong understanding of the market.
PMID- 22046336
TI - Assessing the dream-lag effect for REM and NREM stage 2 dreams.
AB - This study investigates evidence, from dream reports, for memory consolidation
during sleep. It is well-known that events and memories from waking life can be
incorporated into dreams. These incorporations can be a literal replication of
what occurred in waking life, or, more often, they can be partial or indirect.
Two types of temporal relationship have been found to characterize the time of
occurrence of a daytime event and the reappearance or incorporation of its
features in a dream. These temporal relationships are referred to as the day
residue or immediate incorporation effect, where there is the reappearance of
features from events occurring on the immediately preceding day, and the dream
lag effect, where there is the reappearance of features from events occurring 5-7
days prior to the dream. Previous work on the dream-lag effect has used
spontaneous home recalled dream reports, which can be from Rapid Eye Movement
Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses
whether the dream-lag effect occurs only for REM sleep dreams, or for both REM
and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week
before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected
in the laboratory were transcribed and each participant rated the level of
correspondence between every dream report and every diary record. The dream-lag
effect was found for REM but not N2 dreams. Further analysis indicated that this
result was not due to N2 dream reports being shorter, in terms of number of
words, than the REM dream reports. These results provide evidence for a 7-day
sleep-dependent non-linear memory consolidation process that is specific to REM
sleep, and accord with proposals for the importance of REM sleep to emotional
memory consolidation.
PMID- 22046337
TI - Role of the primary motor cortex in the early boost in performance following
mental imagery training.
AB - Recently, it has been suggested that the primary motor cortex (M1) plays a
critical role in implementing the fast and transient post-training phase of motor
skill consolidation, known to yield an early boost in performance. Whether a
comparable early boost in performance occurs following motor imagery (MIM)
training is still unknown. To address this issue, two groups of subjects learned
a finger tapping sequence either by MIM or physical practice (PP). In both
groups, performance increased significantly in the post-training phase when
compared with the pre-training phase and further increased after a 30 min resting
period, indicating that both MIM and PP trainings were equally efficient and
induced an early boost in motor performance. This conclusion was corroborated by
the results of an additional control group. In a second experiment, we then
investigated the causal role of M1 in implementing the early boost process
resulting from MIM training. To do so, we inhibited M1 by applying a continuous
theta-burst stimulation (cTBS) in healthy volunteers just after they learnt, by
MIM, the same finger-tapping task as in Experiment #1. As a control, cTBS was
applied over the vertex of subjects who underwent the same experiment. We found
that cTBS applied over M1 selectively abolished the early boost process
subsequent to MIM training. Altogether, the present study provides evidence that
MIM practice induces an early boost in performance and demonstrates that M1 is
causally involved in this process. These findings further divulge some degree of
behavioral and neuronal similitude between MIM and PP.
PMID- 22046338
TI - An in vivo platform for tumor biomarker assessment.
AB - Tumor biomarkers provide a quantitative tool for following tumor progression and
response to therapy. However, investigations of clinically useful tumor
biomarkers are time-consuming, costly, and limited by patient and tumor
heterogeneity. In addition, assessment of biomarkers as indicators of therapy
response is confounded by the concomitant use of multiple therapeutic
interventions. Herein we report our use of a clinically relevant orthotopic
animal model of malignant pleural mesothelioma for investigating tumor
biomarkers. Utilizing multi-modality imaging with correlative histopathology, we
demonstrate the utility and accuracy of the mouse model in investigating tumor
biomarkers--serum soluble mesothelin-related peptide (SMRP) and osteopontin
(OPN). This model revealed percentage change in SMRP level to be an accurate
biomarker of tumor progression and therapeutic response--a finding consistent
with recent clinical studies. This in vivo platform demonstrates the advantages
of a validated mouse model for the timely and cost-effective acceleration of
human biomarker translational research.
PMID- 22046339
TI - Protective role of hydrogen sulfide against noise-induced cochlear damage: a
chronic intracochlear infusion model.
AB - BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise
induced hearing loss (NIHL). The timely regulation of cochlear perfusion
determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has
attracted increasing interest as a vasodilator in cardiovascular systems. This
study identified the role of H(2)S in cochlear blood flow regulation and noise
protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of
the H(2)S synthetase cystathionine-gamma-lyase (CSE) in the rat cochlea was
examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels
varied according to the duration of noise exposure. A chronic intracochlear
infusion model was built and artificial perilymph (AP), NaHS or DL
propargylglycine (PPG) were locally administered. Local sodium hydrosulfide
(NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear
morphological damage and hearing loss were alleviated in the NaHS group as
measured by conventional auditory brainstem response (ABR), cochlear scanning
electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage
of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results
suggest that H(2)S plays an important role in the regulation of cochlear blood
flow and the protection against noise. Further studies may identify a new
preventive and therapeutic perspective on NIHL and other blood supply-related
inner ear diseases.
PMID- 22046340
TI - Exploring the diversity of Gardnerella vaginalis in the genitourinary tract
microbiota of monogamous couples through subtle nucleotide variation.
AB - BACKGROUND: Bacterial vaginosis (BV) is an enigmatic disease of unknown origin
that affects a large percentage of women. The vaginal microbiota of women with BV
is associated with serious sequelae, including abnormal pregnancies. The etiology
of BV is not fully understood, however, it has been suggested that it is
transmissible, and that G. vaginalis may be an etiological agent. Studies using
enzymatic assays to define G. vaginalis biotypes, as well as more recent genomic
comparisons of G. vaginalis isolates from symptomatic and asymptomatic women,
suggest that particular G. vaginalis strains may play a key role in the
pathogenesis of BV. METHODOLOGY/PRINCIPAL FINDINGS: To explore G. vaginalis
diversity, distribution and sexual transmission, we developed a Shannon entropy
based method to analyze low-level sequence variation in 65,710 G. vaginalis 16S
rRNA gene segments that were PCR-amplified from vaginal samples of 53 monogamous
women and from urethral and penile skin samples of their male partners. We
observed a high degree of low-level diversity among G. vaginalis sequences with a
total of 46 unique sequence variants (oligotypes), and also found strong
correlations of these oligotypes between sexual partners. Even though Gram stain
defined normal and some Gram stain-defined intermediate oligotype profiles
clustered together in UniFrac analysis, no single G. vaginalis oligotype was
found to be specific to BV or normal vaginal samples. CONCLUSIONS: This study
describes a novel method for investigating G. vaginalis diversity at a low level
of taxonomic discrimination. The findings support cultivation-based studies that
indicate sexual partners harbor the same strains of G. vaginalis. This study also
highlights the fact that a few, reproducible nucleotide variations within the 16S
rRNA gene can reveal clinical or epidemiological associations that would be
missed by genus-level or species-level categorization of 16S rRNA data.
PMID- 22046341
TI - Selective algicidal action of peptides against harmful algal bloom species.
AB - Recently, harmful algal bloom (HAB), also termed "red tide", has been recognized
as a serious problem in marine environments according to climate changes
worldwide. Many novel materials or methods to prevent HAB have not yet been
employed except for clay dispersion, in which can the resulting sedimentation on
the seafloor can also cause alteration in marine ecology or secondary
environmental pollution. In the current study, we investigated that antimicrobial
peptide have a potential in controlling HAB without cytotoxicity to harmless
marine organisms. Here, antimicrobial peptides are proposed as new algicidal
compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent
antimicrobial activity via pore forming action in plasma membrane showed that
HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and
induced the efflux of intracellular components. Against raphidoflagellate such as
Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing
action in cell membranes at 1~4 uM within 2 min. Comparatively, its lysing
effects occurred at 8 uM within 1 h in dinoflagellate such as Cochlodium
polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action
induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary,
this peptide was not effective against Skeletonema costatum, harmless algal cell,
even at 256 uM, moreover, it killed only H. akashiwo or C. marina in co
cultivation with S. costatum, indicating to its selective algicidal activity
between harmful and harmless algal cells. The peptide was non-hemolytic against
red blood cells of Sebastes schlegeli, the black rockfish, at 120 uM. HAB cells
were quickly and selectively lysed following treatment of antimicrobial peptides
without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides
examined in our study appear to have much potential in effectively controlling
HAB with minimal impact on marine ecology.
PMID- 22046342
TI - The CDKN2A G500 allele is more frequent in GBM patients with no defined telomere
maintenance mechanism tumors and is associated with poorer survival.
AB - Prognostic markers for glioblastoma multiforme (GBM) are important for patient
management. Recent advances have identified prognostic markers for GBMs that use
telomerase or the alternative lengthening of telomeres (ALT) mechanism for
telomere maintenance. Approximately 40% of GBMs have no defined telomere
maintenance mechanism (NDTMM), with a mixed survival for affected individuals.
This study examined genetic variants in the cyclin-dependent kinase inhibitor 2A
(CDKN2A) gene that encodes the p16(INK4a) and p14(ARF) tumor suppressors, and the
isocitrate dehydrogenase 1 (IDH1) gene as potential markers of survival for 40
individuals with NDTMM GBMs (telomerase negative and ALT negative by standard
assays), 50 individuals with telomerase, and 17 individuals with ALT positive
tumors. The analysis of CDKN2A showed NDTMM GBMs had an increased minor allele
frequency for the C500G (rs11515) polymorphism compared to those with telomerase
and ALT positive GBMs (p = 0.002). Patients with the G500 allele had reduced
survival that was independent of age, extent of surgery, and treatment. In the
NDTMM group G500 allele carriers had increased loss of CDKN2A gene dosage
compared to C500 homozygotes. An analysis of IDH1 mutations showed the R132H
mutation was associated with ALT positive tumors, and was largely absent in NDTMM
and telomerase positive tumors. In the ALT positive tumors cohort, IDH1 mutations
were associated with a younger age for the affected individual. In conclusion,
the G500 CDKN2A allele was associated with NDTMM GBMs from older individuals with
poorer survival. Mutations in IDH1 were not associated with NDTMM GBMs, and
instead were a marker for ALT positive tumors in younger individuals.
PMID- 22046343
TI - A broad set of different llama antibodies specific for a 16 kDa heat shock
protein of Mycobacterium tuberculosis.
AB - BACKGROUND: Recombinant antibodies are powerful tools in engineering of novel
diagnostics. Due to the small size and stable nature of llama antibody domains
selected antibodies can serve as a detection reagent in multiplexed and sensitive
assays for M. tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Antibodies for
Mycobacterium tuberculosis (M. tb) recognition were raised in Alpaca, and, by
phage display, recombinant variable domains of heavy-chain antibodies (VHH)
binding to M. tuberculosis antigens were isolated. Two phage display selection
strategies were followed: one direct selection using semi-purified protein
antigen, and a depletion strategy with lysates, aiming to avoid cross-reaction to
other mycobacteria. Both panning methods selected a set of binders with widely
differing complementarity determining regions. Selected recombinant VHHs were
produced in E. coli and shown to bind immobilized lysate in direct Enzymelinked
Immunosorbent Assay (ELISA) tests and soluble antigen by surface plasmon
resonance (SPR) analysis. All tested VHHs were specific for tuberculosis-causing
mycobacteria (M. tuberculosis, M. bovis) and exclusively recognized an
immunodominant 16 kDa heat shock protein (hsp). The highest affinity VHH had a
dissociation constant (KD) of 4 * 10(-10) M. CONCLUSIONS/SIGNIFICANCE: A broad
set of different llama antibodies specific for 16 kDa heat shock protein of M.
tuberculosis is available. This protein is highly stable and abundant in M.
tuberculosis. The VHH that detect this protein are applied in a robust SPR sensor
for identification of tuberculosis-causing mycobacteria.
PMID- 22046344
TI - The role of endosomal escape and mitogen-activated protein kinases in adenoviral
activation of the innate immune response.
AB - Adenoviral vectors (AdV) activate multiple signaling pathways associated with
innate immune responses, including mitogen-activated protein kinases (MAPKs). In
this study, we investigated how systemically-injected AdVs activate two MAPK
pathways (p38 and ERK) and the contribution of these kinases to AdV-induced
cytokine and chemokine responses in mice. Mice were injected intravenously either
with a helper-dependent Ad2 vector that does not express viral genes or
transgenes, or with the Ad2 mutant ts1, which is defective in endosomal escape.
We found that AdV induced rapid phosphorylation of p38 and ERK as well as a
significant cytokine response, but ts1 failed to activate p38 or ERK and induced
only a limited cytokine response. These results demonstrate that endosomal escape
of virions is a critical step in the induction of these innate pathways and
responses. We then examined the roles of p38 and ERK pathways in the innate
cytokine response by administering specific kinase inhibitors to mice prior to
AdV. The cytokine and chemokine response to AdV was only modestly suppressed by a
p38 inhibitor, while an ERK inhibitor has mixed effects, lowering some cytokines
and elevating others. Thus, even though p38 and ERK are rapidly activated after
i.v. injection of AdV, cytokine and chemokine responses are mostly independent of
these kinases.
PMID- 22046345
TI - Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans
residing in Spain in contrast to the native population.
AB - BACKGROUND: The prevalence of transmitted HIV drug resistance (TDR) is
stabilizing or decreasing in developed countries. However, this trend is not
specifically evaluated among immigrants from regions without well-implemented
antiretroviral strategies. METHODS: TDR trends during 1996-2010 were analyzed
among naive HIV-infected patients in Spain, considering their origin and other
factors. TDR mutations were defined according to the World Health Organization
list. RESULTS: Pol sequence was available for 732 HIV-infected patients: 292
native Spanish, 226 sub-Saharan Africans (SSA), 114 Central-South Americans (CSA)
and 100 from other regions. Global TDR prevalence was 9.7% (10.6% for Spanish,
8.4% for SSA and 7.9% for CSA). The highest prevalences were found for protease
inhibitors (PI) in Spanish (3.1%), for non-nucleoside reverse transcriptase
inhibitors (NNRTI) in SSA (6.5%) and for nucleoside reverse transcriptase
inhibitors (NRTI) in both Spanish and SSA (6.5%). The global TDR rate decreased
from 11.3% in 2004-2006 to 8.4% in 2007-2010. Characteristics related to a
decreasing TDR trend in 2007-10 were Spanish and CSA origin, NRTI- and NNRTI
resistance, HIV-1 subtype B, male sex and infection through injection drug use.
TDR remained stable for PI-resistance, in patients infected through sexual
intercourse and in those carrying non-B variants. However, TDR increased among
SSA and females. K103N was the predominant mutation in all groups and periods.
CONCLUSION: TDR prevalence tended to decrease among HIV-infected native Spanish
and Central-South Americans, but it increased up to 13% in sub-Saharan immigrants
in 2007-2010. These results highlight the importance of a specific TDR
surveillance among immigrants to prevent future therapeutic failures, especially
when administering NNRTIs.
PMID- 22046346
TI - Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib.
AB - BACKGROUND: Overexpression of the ERBB2 kinase is observed in about one-third of
breast cancer patients and the dual ERBB1/ERBB2 kinase inhibitor lapatinib was
recently approved for the treatment of advanced ERBB2-positive breast cancer.
Mutations in the ERBB2 receptor have recently been reported in breast cancer at
diagnosis and also in gastric, colorectal and lung cancer. These mutations may
have an impact on the clinical responses achieved with lapatinib in breast cancer
and may also have a potential impact on the use of lapatinib in other solid
cancers. However, the sensitivity of lapatinib towards clinically observed ERBB2
mutations is not known. METHODOLOGY/PRINCIPAL FINDINGS: We cloned a panel of 8
clinically observed ERBB2 mutations, established stable cell lines and
characterized their sensitivity towards lapatinib and alternative ERBB2
inhibitors. Both lapatinib-sensitive and lapatinib-resistant ERBB2 mutations were
observed. Interestingly, we were able to generate lapatinib resistance mutations
in wt-ERBB2 cells incubated with lapatinib for prolonged periods of time. This
indicates that these resistance mutations may also cause secondary resistance in
lapatinib-treated patients. Lapatinib-resistant ERBB2 mutations were found to be
highly resistant towards AEE788 treatment but remained sensitive towards the dual
irreversible inhibitors CL-387785 and WZ-4002. CONCLUSIONS/SIGNIFICANCE: Patients
harbouring certain ERBB2 kinase domain mutations at diagnosis may not benefit
from lapatinib treatment. Moreover, secondary lapatinib resistance may develop
due to kinase domain mutations. Irreversible ERBB2 inhibitors may offer
alternative treatment options for breast cancer and other solid tumor patients
harbouring lapatinib resistance mutations. In addition, these inhibitors may be
of interest in the scenario of secondary lapatinib resistance.
PMID- 22046347
TI - Differential effects of accumbens core vs. shell lesions in a rat concurrent
conditioned place preference paradigm for cocaine vs. social interaction.
AB - BACKGROUND: A main challenge in the therapy of drug dependent individuals is to
help them reactivate interest in non-drug-associated activities. Among these
activities, social interaction is doubly important because treatment adherence
itself depends on it. We previously developed a rat experimental model based on
the conditioned place preference (CPP) paradigm in which only four 15-min
episodes of social interaction with a gender- and weight-matched male conspecific
(i) reversed CPP from cocaine to social interaction despite continuing cocaine
training and (ii) prevented the reinstatement of cocaine CPP. In the present
study, we investigated if the two subregions of the nucleus accumbens (Acb),
i.e., the core (AcbC) and the shell (AcbSh), would differentially affect CPP for
cocaine vs social interaction. METHODOLOGY/PRINCIPAL FINDINGS: Animals were
concurrently trained for CPP pairing cocaine with one compartment and social
interaction with the other (i.e., mutually exclusive stimulus presentation during
training). Excitotoxic lesioning of the AcbC or the BLA shifted CPP toward social
interaction, whereas AcbSh inactivation shifted CPP toward cocaine. CONCLUSIONS:
Overall, our findings suggest that inactivation of the AcbC or the BLA is
sufficient to shift CPP away from a drug of abuse toward social interaction.
Lesioning the AcbSh produced the opposite effect.
PMID- 22046348
TI - Fishing in the dark: a pursuit-diving seabird modifies foraging behaviour in
response to nocturnal light levels.
AB - Visual predators tend not to hunt during periods when efficiency is compromised
by low light levels. Yet common murres, a species considered a diurnal visual
predator, frequently dive at night. To study foraging of murres under different
light conditions, we used a combination of archival tagging methods and
astronomical models to assess relationships between diving behaviour and light
availability. During diurnal and crepuscular periods, murres used a wide range of
the water column (2-177 m), foraging across light intensities that spanned
several orders of magnitude (10(3)-10(-10) Wm(-2)). Through these periods, they
readily dived under conditions equivalent to ambient moonlight (~10(-4) Wm(-2))
but rarely under conditions equivalent to starlight (~10(-8) Wm(-2)). At night,
murres readily foraged during both moonlit and starlit periods, and diving depth
and efficiency increased with nocturnal light intensity, suggesting that night
diving is at least partially visually guided. Whether visually guided foraging is
possible during starlit periods is less clear. Given the dense prey landscape
available, random-walk simulations suggest that murres could benefit from random
prey encounters. We hypothesise that murres foraging through starlit periods rely
either on close-range visual or possibly nonvisual cues to acquire randomly
encountered prey. This research highlights the flexibility of breeding common
murres and raises questions about the strategies and mechanisms birds use to find
prey under very low light conditions.
PMID- 22046349
TI - Toll-like receptor 3 regulates neural stem cell proliferation by modulating the
Sonic Hedgehog pathway.
AB - Toll-like receptor 3 (TLR3) signaling has been implicated in neural
stem/precursor cell (NPC) proliferation. However, the molecular mechanisms
involved, and their relationship to classical TLR-mediated innate immune
pathways, remain unknown. Here, we report investigation of the mechanics of TLR3
signaling in neurospheres comprised of epidermal growth factor (EGF)-responsive
NPC isolated from murine embryonic cerebral cortex of C57BL/6 (WT) or TLR3
deficient (TLR3(-/-)) mice. Our data indicate that the TLR3 ligand polyinosinic
polycytidylic acid (PIC) negatively regulates NPC proliferation by inhibiting
Sonic Hedgehog (Shh) signaling, that PIC induces apoptosis in association with
inhibition of Ras-ERK signaling and elevated expression of Fas, and that these
effects are TLR3-dependent, suggesting convergent signaling between the Shh and
TLR3 pathways.
PMID- 22046350
TI - Predicting residue-residue contacts and helix-helix interactions in transmembrane
proteins using an integrative feature-based random forest approach.
AB - Integral membrane proteins constitute 25-30% of genomes and play crucial roles in
many biological processes. However, less than 1% of membrane protein structures
are in the Protein Data Bank. In this context, it is important to develop
reliable computational methods for predicting the structures of membrane
proteins. Here, we present the first application of random forest (RF) for
residue-residue contact prediction in transmembrane proteins, which we term as
TMhhcp. Rigorous cross-validation tests indicate that the built RF models provide
a more favorable prediction performance compared with two state-of-the-art
methods, i.e., TMHcon and MEMPACK. Using a strict leave-one-protein-out
jackknifing procedure, they were capable of reaching the top L/5 prediction
accuracies of 49.5% and 48.8% for two different residue contact definitions,
respectively. The predicted residue contacts were further employed to predict
interacting helical pairs and achieved the Matthew's correlation coefficients of
0.430 and 0.424, according to two different residue contact definitions,
respectively. To facilitate the academic community, the TMhhcp server has been
made freely accessible at http://protein.cau.edu.cn/tmhhcp.
PMID- 22046351
TI - Nebulisation of receptor-targeted nanocomplexes for gene delivery to the airway
epithelium.
AB - BACKGROUND: Gene therapy mediated by synthetic vectors may provide opportunities
for new treatments for cystic fibrosis (CF) via aerosolisation. Vectors for CF
must transfect the airway epithelium efficiently and not cause inflammation so
they are suitable for repeated dosing. The inhaled aerosol should be deposited in
the airways since the cystic fibrosis transmembrane conductance regulator gene
(CFTR) is expressed predominantly in the epithelium of the submucosal glands and
in the surface airway epithelium. The aim of this project was to develop an
optimised aerosol delivery approach applicable to treatment of CF lung disease by
gene therapy. METHODOLOGY: The vector suspension investigated in this study
comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that
self-assemble by electrostatic interactions to form a receptor-targeted
nanocomplex (RTN) of approximately 150 nm with a cationic surface charge of +50
mV. The aerodynamic properties of aerosolised nanocomplexes produced with three
different nebulisers were compared by determining aerosol deposition in the
different stages of a Next Generation Pharmaceutical Impactor (NGI). We also
investigated the yield of intact plasmid DNA by agarose gel electrophoresis and
densitometry, and transfection efficacies in vitro and in vivo. RESULTS: RTNs
nebulised with the AeroEclipse II BAN were the most effective, compared to other
nebulisers tested, for gene delivery both in vitro and in vivo. The biophysical
properties of the nanocomplexes were unchanged after nebulisation while the
deposition of RTNs suggested a range of aerosol aerodynamic sizes between 5.5 um
1.4 um cut off (NGI stages 3-6) compatible with deposition in the central and
lower airways. CONCLUSIONS: RTNs showed their ability at delivering genes via
nebulisation, thus suggesting their potential applications for therapeutic
interventions of cystic fibrosis and other respiratory disorders.
PMID- 22046352
TI - Sox9 transcriptionally represses Spp1 to prevent matrix mineralization in
maturing heart valves and chondrocytes.
AB - Sox9 is an SRY-related transcription factor required for expression of
cartilaginous genes in the developing skeletal system and heart valve structures.
In contrast to positively regulating cartilaginous matrix, Sox9 also negatively
regulates matrix mineralization associated with bone formation. While the
transcriptional activation of Sox9 target genes during chondrogenesis has been
characterized, the mechanisms by which Sox9 represses osteogenic processes are
not so clear. Using ChIP-on-chip and luciferase assays we show that Sox9 binds
and represses transactivation of the osteogenic glycoprotein Spp1. In addition,
Sox9 knockdown in post natal mouse heart valve explants and rib chondrocyte
cultures promotes Spp1 expression and matrix mineralization, while attenuating
expression of cartilage genes Type II Collagen and Cartilage Link Protein.
Further, we show that Spp1 is required for matrix mineralization induced by Sox9
knockdown. These studies provide insights into the molecular mechanisms by which
Sox9 prevents pathologic matrix mineralization in tissues that must remain
cartilaginous.
PMID- 22046353
TI - Decidual cell polyploidization necessitates mitochondrial activity.
AB - Cellular polyploidy has been widely reported in nature, yet its developmental
mechanism and function remain poorly understood. In the present study, to better
define the aspects of decidual cell polyploidy, we isolated pure polyploid and
non-polyploid decidual cell populations from the in vivo decidual bed. Three
independent RNA pools prepared for each population were then subjected to the
Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data
revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the
polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR
and in situ hybridization results indeed confirmed differential expressional
regulation of several genes between the two populations. Based on functional
enrichment analyses, up-regulated polyploidy genes appeared to implicate several
functions, which primarily include cell/nuclear division, ATP binding, metabolic
process, and mitochondrial activity, whereas that of down-regulated genes
primarily included apoptosis and immune processes. Further analyses of genes that
are related to mitochondria and bi-nucleation showed differential and regional
expression within the decidual bed, consistent with the pattern of polyploidy.
Consistently, studies revealed a marked induction of mitochondrial mass and ATP
production in polyploid cells. The inhibition of mitochondrial activity by
various pharmacological inhibitors, as well as by gene-specific targeting using
siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi
nucleation development during in vitro stromal cell decidualization, suggesting
mitochondria play a major role in positive regulation of decidual cell
polyploidization. Collectively, analyses of unique polyploidy markers and
molecular signaling networks may be useful to further characterize functional
aspects of decidual cell polyploidy at the site of implantation.
PMID- 22046354
TI - Intracellular kinases mediate increased translation and secretion of netrin-1
from renal tubular epithelial cells.
AB - BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced
after tissue injury, and may serve as a marker of injury. However, the regulation
of netrin-1 production is not unknown. Current study was carried out in mouse and
mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate
netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS:
Ischemia reperfusion injury of the kidney was induced in mice by clamping renal
pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular
epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide,
glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified
by real time RT-PCR and protein production was quantified using an ELISA kit.
Cellular stress induced a large increase in netrin-1 production without increase
in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates
the drug induced netrin-1 mRNA translation increase without altering mRNA
stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed
at the translational level and MAPK activation leads to rapid translation of
netrin-1 mRNA in the kidney tubular epithelial cells.
PMID- 22046355
TI - Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC
inflammasome-mediated activation of caspase-1.
AB - IL-1beta and IL-18 are proinflammatory cytokines that contribute to renal immune
complex disease, but whether IL-1beta and IL-18 are mediators of intrinsic
glomerular inflammation is unknown. In contrast to other cytokines the secretion
of IL-1beta and IL-18 requires a second stimulus that activates the inflammasome
ASC-caspase-1 pathway to cleave pro-IL-1beta and -IL-18 into their mature and
secretable forms. As the NLRP3 inflammasome and caspase-1 were shown to
contribute to postischemic and postobstructive tubulointerstitial inflammation,
we hypothesized a similar role for NLRP3, ASC, and caspase-1 in glomerular
immunopathology. This concept was supported by the finding that lack of IL-1R1
reduced antiserum-induced focal segmental necrosis, crescent formation, and
tubular atrophy when compared to wildtype mice. Lack of IL-18 reduced tubular
atrophy only. However, NLRP3-, ASC- or caspase-1-deficiency had no significant
effect on renal histopathology or proteinuria of serum nephritis. In vitro
studies with mouse glomeruli or mesangial cells, glomerular endothelial cells,
and podocytes did not reveal any pro-IL-1beta induction upon LPS stimulation and
no caspase-1 activation after an additional exposure to the NLRP3 agonist ATP.
Only renal dendritic cells, which reside mainly in the tubulointerstitium,
expressed pro-IL-1beta and were able to activate the NLRP3-caspase-1 axis and
secrete mature IL-1beta. Together, the NLRP3-ASC-caspase-1 axis does not
contribute to intrinsic glomerular inflammation via glomerular parenchymal cells
as these cannot produce IL-1beta during sterile inflammation.
PMID- 22046356
TI - Individual analyses of Levy walk in semi-free ranging Tonkean macaques (Macaca
tonkeana).
AB - Animals adapt their movement patterns to their environment in order to maximize
their efficiency when searching for food. The Levy walk and the Brownian walk are
two types of random movement found in different species. Studies have shown that
these random movements can switch from a Brownian to a Levy walk according to the
size distribution of food patches. However no study to date has analysed how
characteristics such as sex, age, dominance or body mass affect the movement
patterns of an individual. In this study we used the maximum likelihood method to
examine the nature of the distribution of step lengths and waiting times and
assessed how these distributions are influenced by the age and the sex of group
members in a semi free-ranging group of ten Tonkean macaques. Individuals highly
differed in their activity budget and in their movement patterns. We found an
effect of age and sex of individuals on the power distribution of their step
lengths and of their waiting times. The males and old individuals displayed a
higher proportion of longer trajectories than females and young ones. As regards
waiting times, females and old individuals displayed higher rates of long
stationary periods than males and young individuals. These movement patterns
resembling random walks can probably be explained by the animals moving from one
location to other known locations. The power distribution of step lengths might
be due to a power distribution of food patches in the enclosure while the power
distribution of waiting times might be due to the power distribution of the patch
sizes.
PMID- 22046357
TI - N-cofilin can compensate for the loss of ADF in excitatory synapses.
AB - Actin plays important roles in a number of synaptic processes, including synaptic
vesicle organization and exocytosis, mobility of postsynaptic receptors, and
synaptic plasticity. However, little is known about the mechanisms that control
actin at synapses. Actin dynamics crucially depend on LIM kinase 1 (LIMK1) that
controls the activity of the actin depolymerizing proteins of the ADF/cofilin
family. While analyses of mouse mutants revealed the importance of LIMK1 for both
pre- and postsynaptic mechanisms, the ADF/cofilin family member n-cofilin appears
to be relevant merely for postsynaptic plasticity, and not for presynaptic
physiology. By means of immunogold electron microscopy and immunocytochemistry,
we here demonstrate the presence of ADF (actin depolymerizing factor), a close
homolog of n-cofilin, in excitatory synapses, where it is particularly enriched
in presynaptic terminals. Surprisingly, genetic ablation of ADF in mice had no
adverse effects on synapse structure or density as assessed by electron
microscopy and by the morphological analysis of Golgi-stained hippocampal
pyramidal cells. Moreover, a series of electrophysiological recordings in acute
hippocampal slices revealed that presynaptic recruitment and exocytosis of
synaptic vesicles as well as postsynaptic plasticity were unchanged in ADF mutant
mice. The lack of synaptic defects may be explained by the elevated n-cofilin
levels observed in synaptic structures of ADF mutants. Indeed, synaptic actin
regulation was impaired in compound mutants lacking both ADF and n-cofilin, but
not in ADF single mutants. From our results we conclude that n-cofilin can
compensate for the loss of ADF in excitatory synapses. Further, our data suggest
that ADF and n-cofilin cooperate in controlling synaptic actin content.
PMID- 22046358
TI - Epigenetic changes with dietary soy in cynomolgus monkeys.
AB - Nutritional interventions are important alternatives for reducing the prevalence
of many chronic diseases. Soy is a good source of protein that contains
isoflavones, including genistein and daidzein, and may alter the risk of obesity,
Type 2 diabetes, osteoporosis, cardiovascular disease, and reproductive cancers.
We have shown previously in nonhuman primates that soy protein containing
isoflavones leads to improved body weight, insulin sensitivity, lipid profiles,
and atherosclerosis compared to protein without soy isoflavones (casein), and
does not increase the risk of cancer. Since genistein has been shown to alter DNA
methylation, we compared the methylation profiles of cynomolgus monkeys, from
multiple tissues, eating two high-fat, typical American diets (TAD) with similar
macronutrient contents, with or without soy protein. DNA methylation status was
successfully determined for 80.6% of the probes in at least one tissue using
Illumina's HumanMethylation27 BeadChip. Overall methylation increased in liver
and muscle tissue when monkeys switched from the TAD-soy to the TAD-casein diets.
Genes involved in epigenetic processes, specifically homeobox genes (HOXA5,
HOXA11, and HOXB1), and ABCG5 were among those that changed between diets. These
data support the use of the HumanMethylation27 BeadChip in cynomolgus monkeys and
identify epigenetic changes associated with dietary interventions with soy
protein that may potentially affect the etiology of complex diseases.
PMID- 22046359
TI - Novel adiponectin variants identified in type 2 diabetic patients reveal
multimerization and secretion defects.
AB - ADIPOQ, encoding adiponectin, is a candidate gene for type 2 diabetes (T2D)
identified by genome-wide linkage analyses with supporting evidence showing the
protein function in sensitizing insulin actions. In an endeavor to characterize
candidate genes causing T2D in Thai patients, we identified 10 novel ADIPOQ
variations, several of which were non-synonymous variations observed only in the
patients. To examine the impact of these non-synonymous variations on adiponectin
structure and biochemical characteristics, we conducted a structural analysis of
the wild-type and variant proteins by in silico modeling and further
characterized biochemical properties of the variants with predicted structural
abnormalities from the modeling by molecular and biochemical studies. The
recombinant plasmids containing wild-type and variant ADIPOQ cDNAs derived from
the variations identified by our study (R55H, R112H, and R131H) and previous work
(G90S and R112C) were constructed and transiently expressed and co-expressed in
cultured HEK293T cells to investigate their oligomerization, interaction, and
secretion. We found that the novel R55H variant impaired protein multimerization
but it did not exert the effect over the co-expressed wild-type protein while
novel R131H variant impaired protein secretion and also affected the co-expressed
wild-type protein in a dominant negative fashion. The R131H variant could traffic
from the endoplasmic reticulum to the Golgi, trans-Golgi network, and early
endosome but could not be secreted. The R131H variant was likely to be degraded
through the lysosomal system and inhibition of its degradation rescued the
variant protein from secretion defect. We have shown the possibility of using in
silico modeling for predicting the effect of amino acid substitution on
adiponectin oligomerization. This is also the first report that demonstrates a
dominant negative effect of the R131H variant on protein secretion and the
possibility of using protein degradation inhibitors as therapeutic agents in the
patients carrying adiponectin variants with secretion defect.
PMID- 22046360
TI - Host centrality in food web networks determines parasite diversity.
AB - BACKGROUND: Parasites significantly alter topological metrics describing food web
structure, yet few studies have explored the relationship between food web
topology and parasite diversity. METHODS/PRINCIPAL FINDINGS: This study uses
quantitative metrics describing network structure to investigate the relationship
between the topology of the host food web and parasite diversity. Food webs were
constructed for four restored brackish marshes that vary in species diversity,
time post restoration and levels of parasitism. Our results show that the
topology of the food web in each brackish marsh is highly nested, with clusters
of generalists forming a distinct modular structure. The most consistent
predictors of parasite diversity within a host were: trophic generality, and
eigenvector centrality. These metrics indicate that parasites preferentially
colonise host species that are highly connected, and within modules of tightly
interacting species in the food web network. CONCLUSIONS/SIGNIFICANCE: These
results suggest that highly connected free-living species within the food web may
represent stable trophic relationships that allow for the persistence of complex
parasite life cycles. Our data demonstrate that the structure of host food webs
can have a significant effect on the establishment of parasites, and on the
potential for evolution of complex parasite life cycles.
PMID- 22046361
TI - Evidence for retrogene origins of the prion gene family.
AB - The evolutionary origin of prion genes, only known to exist in the vertebrate
lineage, had remained elusive until recently. Following a lead from interactome
investigations of the murine prion protein, our previous bioinformatic analyses
revealed the evolutionary descent of prion genes from an ancestral ZIP metal ion
transporter. However, the molecular mechanism of evolution remained unexplored.
Here we present a computational investigation of this question based on sequence,
intron-exon, synteny and pseudogene analyses. Our data suggest that during the
emergence of metazoa, a cysteine-flanked core domain was modularly inserted, or
arose de novo, in a preexisting ZIP ancestor gene to generate a prion-like
ectodomain in a subbranch of ZIP genes. Approximately a half-billion years later,
a genomic insertion of a spliced transcript coding for such a prion-like ZIP
ectodomain may have created the prion founder gene. We document that similar
genomic insertions involving ZIP transcripts, and probably relying on
retropositional elements, have indeed occurred more than once throughout
evolution.
PMID- 22046362
TI - The transcriptome of the reference potato genome Solanum tuberosum Group Phureja
clone DM1-3 516R44.
AB - Advances in molecular breeding in potato have been limited by its complex
biological system, which includes vegetative propagation, autotetraploidy, and
extreme heterozygosity. The availability of the potato genome and accompanying
gene complement with corresponding gene structure, location, and functional
annotation are powerful resources for understanding this complex plant and
advancing molecular breeding efforts. Here, we report a reference for the potato
transcriptome using 32 tissues and growth conditions from the doubled monoploid
Solanum tuberosum Group Phureja clone DM1-3 516R44 for which a genome sequence is
available. Analysis of greater than 550 million RNA-Seq reads permitted the
detection and quantification of expression levels of over 22,000 genes.
Hierarchical clustering and principal component analyses captured the biological
variability that accounts for gene expression differences among tissues
suggesting tissue-specific gene expression, and genes with tissue or condition
restricted expression. Using gene co-expression network analysis, we identified
18 gene modules that represent tissue-specific transcriptional networks of major
potato organs and developmental stages. This information provides a powerful
resource for potato research as well as studies on other members of the
Solanaceae family.
PMID- 22046363
TI - Responses of peripheral blood flow to acute hypoxia and hyperoxia as measured by
optical microangiography.
AB - Oxygen availability is regarded as a critical factor to metabolically regulate
systemic blood flow. There is a debate as to how peripheral blood flow (PBF) is
affected and modulated during hypoxia and hyperoxia; however in vivo evaluating
of functional PBF under oxygen-related physiological perturbation remains
challenging. Microscopic observation, the current frequently used imaging
modality for PBF characterization often involves the use of exogenous contrast
agents, which would inevitably perturb the intrinsic physiologic responses of
microcirculation being investigated. In this paper, optical micro-angiography
(OMAG) was employed that uses intrinsic optical scattering signals backscattered
from blood flows for imaging PBF in skeletal muscle challenged by the alteration
of oxygen concentration. By utilizing optical reflectance signals, we
demonstrated that OMAG is able to show the response of hemodynamic activities
upon acute hypoxia and hyperoxia, including the modulation of macrovascular
caliber, microvascular density, and flux regulation within different sized
vessels within skeletal muscle in mice in vivo. Our results suggest that OMAG is
a promising tool for in vivo monitoring of functional macro- or micro-vascular
responses within peripheral vascular beds.
PMID- 22046364
TI - The fission yeast RNA binding protein Mmi1 regulates meiotic genes by controlling
intron specific splicing and polyadenylation coupled RNA turnover.
AB - The polyA tails of mRNAs are monitored by the exosome as a quality control
mechanism. We find that fission yeast, Schizosaccharomyces pombe, adopts this RNA
quality control mechanism to regulate a group of 30 or more meiotic genes at the
level of both splicing and RNA turnover. In vegetative cells the RNA binding
protein Mmi1 binds to the primary transcripts of these genes. We find the novel
motif U(U/C/G)AAAC highly over-represented in targets of Mmi1. Mmi1 can
specifically regulate the splicing of particular introns in a transcript: it
inhibits the splicing of introns that are in the vicinity of putative Mmi1
binding sites, while allowing the splicing of other introns that are far from
such sites. In addition, binding of Mmi1, particularly near the 3' end, alters 3'
processing to promote extremely long polyA tails of up to a kilobase. The
hyperadenylated transcripts are then targeted for degradation by the nuclear
exonuclease Rrp6. The nuclear polyA binding protein Pab2 assists this
hyperadenylation-mediated RNA decay. Rrp6 also targets other hyperadenylated
transcripts, which become hyperadenylated in an unknown, but Mmi1-independent
way. Thus, hyperadenylation may be a general signal for RNA degradation. In
addition, binding of Mmi1 can affect the efficiency of 3' cleavage. Inactivation
of Mmi1 in meiosis allows meiotic expression, through splicing and RNA
stabilization, of at least 29 target genes, which are apparently constitutively
transcribed.
PMID- 22046365
TI - Mechanism of acetylcholine receptor cluster formation induced by DC electric
field.
AB - BACKGROUND: The formation of acetylcholine receptor (AChR) cluster is a key event
during the development of the neuromuscular junction. It is induced through the
activation of muscle-specific kinase (MuSK) by the heparan-sulfate proteoglycan
agrin released from the motor axon. On the other hand, DC electric field, a non
neuronal stimulus, is also highly effective in causing AChRs to cluster along the
cathode-facing edge of muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: To
understand its molecular mechanism, quantum dots (QDs) were used to follow the
movement of AChRs as they became clustered under the influence of electric field.
From analyses of trajectories of AChR movement in the membrane, it was concluded
that diffuse receptors underwent Brownian motion until they were immobilized at
sites of cluster formation. This supports the diffusion-mediated trapping model
in explaining AChR clustering under the influence of this stimulus. Disrupting F
actin cytoskeleton assembly and interfering with rapsyn-AChR interaction
suppressed this phenomenon, suggesting that these are integral components of the
trapping mechanism induced by the electric field. Consistent with the idea that
signaling pathways are activated by this stimulus, the localization of tyrosine
phosphorylated forms of AChR beta-subunit and Src was observed at cathodal AChR
clusters. Furthermore, disrupting MuSK activity through the expression of a
kinase-dead form of this enzyme abolished electric field-induced AChR clustering.
CONCLUSIONS: These results suggest that DC electric field as a physical stimulus
elicits molecular reactions in muscle cells in the form of cathodal MuSK
activation in a ligand-free manner to trigger a signaling pathway that leads to
cytoskeletal assembly and AChR clustering.
PMID- 22046366
TI - Reversal of glial and neurovascular markers of unhealthy brain aging by exercise
in middle-aged female mice.
AB - Healthy brain aging and cognitive function are promoted by exercise. The benefits
of exercise are attributed to several mechanisms, many which highlight its
neuroprotective role via actions that enhance neurogenesis, neuronal morphology
and/or neurotrophin release. However, the brain is also composed of glial and
vascular elements, and comparatively less is known regarding the effects of
exercise on these components in the aging brain. Here, we show that aerobic
exercise at mid-age decreased markers of unhealthy brain aging including
astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were
assigned to a sedentary group or provided a running wheel for six weeks. Exercise
decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a
marker of angiogenesis. Brain vascular casts revealed exercise-induced structural
modifications associated with improved endothelial function in the periphery. Our
results suggest that age-related astrocyte hypertrophy/reactivity and myelin
dysregulation are aggravated by a sedentary lifestyle and accompanying reductions
in vascular function. However, these effects appear reversible with exercise
initiated at mid-age. As this period of the lifespan coincides with the
appearance of multiple markers of brain aging, including initial signs of
cognitive decline, it may represent a window of opportunity for intervention as
the brain appears to still possess significant vascular plasticity. These results
may also have particular implications for aging females who are more susceptible
than males to certain risk factors which contribute to vascular aging.
PMID- 22046367
TI - Stigmatising attitudes among people offered home-based HIV testing and
counselling in Blantyre, Malawi: construction and analysis of a stigma scale.
AB - BACKGROUND: HIV/AIDS related stigma is a major barrier to uptake of HIV testing
and counselling (HTC). We assessed the extent of stigmatising attitudes expressed
by participants offered community-based HTC, and their anticipated stigma from
others to assess relationship with HIV test uptake. From these data, we
constructed a brief stigma scale for use around the time of HIV testing. METHODS
AND FINDINGS: Adult members of 60 households in urban Blantyre, Malawi, were
selected using population-weighted random cluster sampling and offered HTC with
the option to self-test before confirmatory HTC. Prior to HTC a 15-item HIV
stigma questionnaire was administered. We used association testing and principal
components analysis (PCA) to construct a scale measure of stigma. Of 226 adults
invited to participate, 216 (95.6%) completed questionnaires and 198/216 (91.7%)
opted to undergo HTC (all self-tested). Stigmatising attitudes were uncommon, but
anticipated stigma was common, especially fearing verbal abuse (22%) or being
abandoned by their partner (11%). Three questions showed little association or
consistency with the remaining 12 stigma questions and were not included in the
final scale. For the 12-question final scale, Cronbach's alpha was 0.75. Level of
stigma was not associated with previously having tested for HIV (p = 0.318) or
agreeing to HTC (p = 0.379), but was associated with expressed worry about being
or becoming HIV infected (p = 0.003). CONCLUSIONS: Anticipated stigma prior to
HTC was common among both men and women. However, the high uptake of HTC suggests
that this did not translate into reluctance to accept community-based testing. We
constructed a brief scale to measure stigma at the time of HIV testing that could
rapidly identify individuals requiring additional support following diagnosis and
monitor the impact of increasing availability of community-based HTC on
prevalence of stigma.
PMID- 22046368
TI - EP receptor expression in human intestinal epithelium and localization relative
to the stem cell zone of the crypts.
AB - There is substantial evidence for PGE2 affecting intestinal epithelial
proliferation. PGE2 is also reported to be involved in the regulation of growth
and differentiation in adult stem cells, both effects mediated by binding to EP
receptors. We have used the Lgr5 as a marker to scrutinize EP-receptor and COX
expression in human intestinal epithelial cells with focus on the stem cell area
of the crypts. Normal tissue from ileum and colon, but also duodenal biopsies
from patients with untreated celiac disease, were investigated by
immunohistochemistry and RT-PCR. The combination of fresh flash-frozen tissue and
laser microdissection made it possible to isolate RNA from the epithelial cell
layer, only. In the small intestine, Lgr5 labels cells are in the +4 position,
while in the colon, Lgr5 positive cells are localized to the crypt bottoms.
Epithelial crypt cells of normal small intestine expressed neither EP-receptor
mRNA nor COX1/2. However, crypt cells in tissue from patients with untreated
celiac disease expressed EP2/4 receptor and COX1 mRNA. In the colon, the
situation was different. Epithelial crypt cells from normal colon were found to
express EP2/4 receptor and COX1/2 transcripts. Thus, there are distinct
differences between normal human small intestine and colon with regard to
expression of EP2/4 receptors and COX1/2. In normal colon tissue, PGE2-mediated
signaling through EP-receptors 2/4 could be involved in regulation of growth and
differentiation of the epithelium, while the lack of EP-receptor expression in
the small intestinal tissue exclude the possibility of a direct effect of PGE2 on
the crypt epithelial cells.
PMID- 22046369
TI - Species-specific codon context rules unveil non-neutrality effects of synonymous
mutations.
AB - BACKGROUND: Codon pair usage (codon context) is a species specific gene primary
structure feature whose evolutionary and functional roles are poorly understood.
The data available show that codon-context has direct impact on both translation
accuracy and efficiency, but one does not yet understand how it affects these two
translation variables or whether context biases shape gene evolution.
METHODOLOGIES/PRINCIPAL FINDINGS: Here we study codon-context biases using a set
of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high
eukaryotes to identify 7 distinct groups of codon context rules. We show that
synonymous mutations, i.e., neutral mutations that occur in synonymous codons of
codon-pairs, are selected to maintain context biases and that non-synonymous
mutations, i.e., non-neutral mutations that alter protein amino acid sequences,
are also under selective pressure to preserve codon-context biases. CONCLUSIONS:
Since in vivo studies provide evidence for a role of codon context on decoding
fidelity in E. coli and for decoding efficiency in mammalian cells, our data
support the hypothesis that, like codon usage, codon context modulates the
evolution of gene primary structure and fine tunes the structure of open reading
frames for high genome translational fidelity and efficiency in the 3 domains of
life.
PMID- 22046370
TI - Evidence of infection with H4 and H11 avian influenza viruses among Lebanese
chicken growers.
AB - Human infections with H5, H7, and H9 avian influenza viruses are well documented.
Exposure to poultry is the most important risk factor for humans becoming
infected with these viruses. Data on human infection with other low pathogenicity
avian influenza viruses is sparse but suggests that such infections may occur.
Lebanon is a Mediterranean country lying under two major migratory birds flyways
and is home to many wild and domestic bird species. Previous reports from this
country demonstrated that low pathogenicity avian influenza viruses are in
circulation but highly pathogenic H5N1 viruses were not reported. In order to
study the extent of human infection with avian influenza viruses in Lebanon, we
carried out a seroprevalence cross-sectional study into which 200 poultry-exposed
individuals and 50 non-exposed controls were enrolled. We obtained their sera and
tested it for the presence of antibodies against avian influenza viruses types H4
through H16 and used a questionnaire to collect exposure data. Our
microneutralization assay results suggested that backyard poultry growers may
have been previously infected with H4 and H11 avian influenza viruses. We
confirmed these results by using a horse red blood cells hemagglutination
inhibition assay. Our data also showed that farmers with antibodies against each
virus type clustered in a small geographic area suggesting that unrecognized
outbreaks among birds may have led to these human infections. In conclusion, this
study suggests that occupational exposure to chicken is a risk factor for
infection with avian influenza especially among backyard growers and that H4 and
H11 influenza viruses may possess the ability to cross the species barrier to
infect humans.
PMID- 22046371
TI - Neural cell 3D microtissue formation is marked by cytokines' up-regulation.
AB - Cells cultured in three dimensional (3D) scaffolds as opposed to traditional two
dimensional (2D) substrates have been considered more physiologically relevant
based on their superior ability to emulate the in vivo environment. Combined with
stem cell technology, 3D cell cultures can provide a promising alternative for
use in cell-based assays or biosensors in non-clinical drug discovery studies. To
advance 3D culture technology, a case has been made for identifying and
validating three-dimensionality biomarkers. With this goal in mind, we conducted
a transcriptomic expression comparison among neural progenitor cells cultured on
2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo
surrogate). Up-regulation of cytokines as a group in 3D and neurospheres was
observed. A group of 13 cytokines were commonly up-regulated in cells cultured in
polystyrene scaffolds and neurospheres, suggesting potential for any or a
combination from this list to serve as three-dimensionality biomarkers. These
results are supportive of further cytokine identification and validation studies
with cells from non-neural tissue.
PMID- 22046372
TI - Increasing antiproliferative properties of endocannabinoids in N1E-115
neuroblastoma cells through inhibition of their metabolism.
AB - The antitumoral properties of endocannabinoids received a particular attention
these last few years. Indeed, these endogenous molecules have been reported to
exert cytostatic, apoptotic and antiangiogenic effects in different tumor cell
lines and tumor xenografts. Therefore, we investigated the cytotoxicity of three
N-acylethanolamines--N-arachidonoylethanolamine (anandamide, AEA), N
palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA)--which were all able
to time- and dose-dependently reduce the viability of murine N1E-115
neuroblastoma cells. Moreover, several inhibitors of FAAH and NAAA, whose
presence was confirmed by RT-PCR in the cell line, induced cell cytotoxicity and
favored the decrease in cell viability caused by N-acylethanolamines. The most
cytotoxic treatment was achieved by the co-incubation of AEA with the selective
FAAH inhibitor URB597, which drastically reduced cell viability partly by
inhibiting AEA hydrolysis and consequently increasing AEA levels. This
combination of molecules synergistically decreased cell proliferation without
inducing cell apoptosis or necrosis. We found that these effects are independent
of cannabinoid, TRPV1, PPARalpha, PPARgamma or GPR55 receptors activation but
seem to occur through a lipid raft-dependent mechanism. These findings further
highlight the interest of targeting the endocannabinoid system to treat cancer.
More particularly, this emphasizes the great potential benefit of designing novel
anti-cancerous therapies based on the association of endocannabinoids and
inhibitors of their hydrolysis.
PMID- 22046373
TI - A Brassica napus lipase locates at the membrane contact sites involved in
chloroplast development.
AB - BACKGROUND: Fatty acids synthesized in chloroplast are transported to endoplasmic
reticulum (ER) for triacylglycerols (TAGs) resembling. The development of
chloroplast also requires lipids trafficking from ER to chloroplast. The membrane
contact sites (MCSs) between ER and chloroplast has been demonstrated to be
involved for the trafficking of lipids and proteins. Lipids trafficking between
ER and chloroplast is often accompanied by lipids interconversion. However, it is
rarely known how lipids interconversion happens during their trafficking.
METHODOLOGY/PRINCIPAL FINDINGS: We cloned a lipase gene from Brassica napus L.,
designated as BnCLIP1. Green fluorescence protein (GFP)-tagged BnCLIP1 was shown
to locate at the MCSs between ER and chloroplasts in tobacco leaves.
Heterogeneous expression of BnCLIP1 in Saccharomyces cerevisiae (pep4) reduced
the total amount of fatty acid. Gas chromatography-mass spectrometry (GC-MS)
analysis revealed that the truncated BnCLIP1 had a substrate preference for C16:0
lipids in Saccharomyces cerevisiae (pep4). To probe the physiological function of
BnCLIP1, two Brassica napus lines with different oil-content were introduced to
investigate the transcript patterns of BnCLIP1 during seed development.
Intriguingly, the transcript level of BnCLIP1 was found to be immediately up
regulated during the natural seed senescence of both lines; the transcription
response of BnCLIP1 in the high oil-content seeds was faster than the lower ones,
suggesting a potential role of BnCLIP1 in affecting seed oil synthesis via
regulating chloroplast integrity. Further researches showed that chemical
disruption of leaf chloroplast also activated the transcription of BnCLIP1.
CONCLUSIONS/SIGNIFICANCE: The findings of this study show that BnCLIP1 encodes a
lipase, localizes at the MCSs and involves in chloroplast development.
PMID- 22046374
TI - Transcriptional and functional analysis of the effects of magnolol: inhibition of
autolysis and biofilms in Staphylococcus aureus.
AB - BACKGROUND: The targeting of Staphylococcus aureus biofilm structures are now
gaining interest as an alternative strategy for developing new types of
antimicrobial agents. Magnolol (MOL) shows inhibitory activity against S. aureus
biofilms and Triton X-100-induced autolysis in vitro, although there are no data
regarding the molecular mechanisms of MOL action in bacteria.
METHODOLOGY/PRINCIPAL FINDINGS: The molecular basis of the markedly reduced
autolytic phenotype and biofilm inhibition triggered by MOL were explored using
transcriptomic analysis, and the transcription of important genes were verified
by real-time RT-PCR. The inhibition of autolysis by MOL was evaluated using
quantitative bacteriolytic assays and zymographic analysis, and antibiofilm
activity assays and confocal laser scanning microscopy were used to elucidate the
inhibition of biofilm formation caused by MOL in 20 clinical isolates or standard
strains. The reduction in cidA, atl, sle1, and lytN transcript levels following
MOL treatment was consistent with the induced expression of their autolytic
repressors lrgA, lrgB, arlR, and sarA. MOL generally inhibited or reversed the
expression of most of the genes involved in biofilm production. The growth of S.
aureus strain ATCC 25923 in the presence of MOL dose-dependently led to decreases
in Triton X-100-induced autolysis, extracellular murein hydrolase activity, and
the amount of extracellular DNA (eDNA). MOL may impede biofilm formation by
reducing the expression of cidA, a murein hydrolase regulator, to inhibit
autolysis and eDNA release, or MOL may directly repress biofilm formation.
CONCLUSIONS/SIGNIFICANCE: MOL shows in vitro antimicrobial activity against
clinical and standard S. aureus strains grown in planktonic and biofilm cultures,
suggesting that the structure of MOL may potentially be used as a basis for the
development of drugs targeting biofilms.
PMID- 22046375
TI - Carrageenans, sulphated polysaccharides of red seaweeds, differentially affect
Arabidopsis thaliana resistance to Trichoplusia ni (cabbage looper).
AB - Carrageenans are a collective family of linear, sulphated galactans found in a
number of commercially important species of marine red alga. These
polysaccharides are known to elicit defense responses in plant and animals and
possess anti-viral properties. We investigated the effect of foliar application
of iota-, kappa- and lambda-carrageenans (representing various levels of
sulphation) on Arabidopsis thaliana in resistance to the generalist insect
Trichoplusia ni (cabbage looper) which is known to cause serious economic losses
in crop plants. Plants treated with iota- and kappa-carrageenan showed reduced
leaf damage, whereas those treated with lambda- carrageenan were similar to that
of the control. In a no-choice test, larval weight was reduced by more than 20%
in iota- and kappa- carrageenan treatments, but unaffected by lambda-carrageenan.
In multiple choice tests, carrageenan treated plants attracted fewer T. ni larvae
by the fourth day following infestation as compared to the control. The
application of carrageenans did not affect oviposition behaviour of T. ni. Growth
of T. ni feeding on an artificial diet amended with carrageenans was not
different from that fed with untreated control diet. iota-carrageenan induced the
expression of defense genes; PR1, PDF1.2, and TI1, but kappa- and lambda
carrageenans did not. Besides PR1, PDF1.2, and TI1, the indole glucosinolate
biosynthesis genes CYP79B2, CYP83B1 and glucosinolate hydrolysing QTL, ESM1 were
up-regulated by iota-carrageenan treatment at 48 h post infestation. Gas
chromatography-mass spectrometry analysis of carrageenan treated leaves showed
increased concentrations of both isothiocyanates and nitriles. Taken together,
these results show that carrageenans have differential effects on Arabidopsis
resistance to T. ni and that the degree of sulphation of the polysaccharide chain
may well mediate this effect.
PMID- 22046376
TI - Effects of elevated CO2 and N addition on growth and N2 fixation of a legume
subshrub (Caragana microphylla Lam.) in temperate grassland in China.
AB - It is well demonstrated that the responses of plants to elevated atmospheric
CO(2) concentration are species-specific and dependent on environmental
conditions. We investigated the responses of a subshrub legume species, Caragana
microphylla Lam., to elevated CO(2) and nitrogen (N) addition using open-top
chambers in a semiarid temperate grassland in northern China for three years.
Measured variables include leaf photosynthetic rate, shoot biomass, root biomass,
symbiotic nitrogenase activity, and leaf N content. Symbiotic nitrogenase
activity was determined by the C(2)H(2) reduction method. Elevated CO(2) enhanced
photosynthesis and shoot biomass by 83% and 25%, respectively, and the
enhancement of shoot biomass was significant only at a high N concentration. In
addition, the photosynthetic capacity of C. microphylla did not show down
regulation under elevated CO(2). Elevated CO(2) had no significant effect on root
biomass, symbiotic nitrogenase activity and leaf N content. Under elevated CO(2),
N addition stimulated photosynthesis and shoot biomass. By contrast, N addition
strongly inhibited symbiotic nitrogenase activity and slightly increased leaf N
content of C. microphylla under both CO(2) levels, and had no significant effect
on root biomass. The effect of elevated CO(2) and N addition on C. microphylla
did not show interannual variation, except for the effect of N addition on leaf N
content. These results indicate that shoot growth of C. microphylla is more
sensitive to elevated CO(2) than is root growth. The stimulation of shoot growth
of C. microphylla under elevated CO(2) or N addition is not associated with
changes in N(2)-fixation. Additionally, elevated CO(2) and N addition interacted
to affect shoot growth of C. microphylla with a stimulatory effect occurring only
under combination of these two factors.
PMID- 22046377
TI - Crystal structure of outer membrane protein NMB0315 from Neisseria meningitidis.
AB - NMB0315 is an outer membrane protein of Neisseria meningitidis serogroup B (NMB)
and a potential candidate for a broad-spectrum vaccine against meningococcal
disease. The crystal structure of NMB0315 was solved by single-wavelength
anomalous dispersion (SAD) at a resolution of 2.4 A and revealed to be a
lysostaphin-type peptidase of the M23 metallopeptidase family. The overall
structure consists of three well-separated domains and has no similarity to any
previously published structure. However, only the topology of the carboxyl
terminal domain is highly conserved among members of this family, and this domain
is a zinc-dependent catalytic unit. The amino-terminal domain of the structure
blocks the substrate binding pocket in the carboxyl-terminal domain, indicating
that the wild-type full-length protein is in an inactive conformational state.
Our studies improve the understanding of the catalytic mechanism of M23
metallopeptidases.
PMID- 22046378
TI - How did the spider cross the river? Behavioral adaptations for river-bridging
webs in Caerostris darwini (Araneae: Araneidae).
AB - BACKGROUND: Interspecific coevolution is well described, but we know
significantly less about how multiple traits coevolve within a species,
particularly between behavioral traits and biomechanical properties of animals'
"extended phenotypes". In orb weaving spiders, coevolution of spider behavior
with ecological and physical traits of their webs is expected. Darwin's bark
spider (Caerostris darwini) bridges large water bodies, building the largest
known orb webs utilizing the toughest known silk. Here, we examine C. darwini web
building behaviors to establish how bridge lines are formed over water. We also
test the prediction that this spider's unique web ecology and architecture
coevolved with new web building behaviors. METHODOLOGY: We observed C. darwini in
its natural habitat and filmed web building. We observed 90 web building events,
and compared web building behaviors to other species of orb web spiders.
CONCLUSIONS: Caerostris darwini uses a unique set of behaviors, some unknown in
other spiders, to construct its enormous webs. First, the spiders release
unusually large amounts of bridging silk into the air, which is then carried
downwind, across the water body, establishing bridge lines. Second, the spiders
perform almost no web site exploration. Third, they construct the orb capture
area below the initial bridge line. In contrast to all known orb-weavers, the web
hub is therefore not part of the initial bridge line but is instead built de
novo. Fourth, the orb contains two types of radial threads, with those in the
upper half of the web doubled. These unique behaviors result in a giant, yet
rather simplified web. Our results continue to build evidence for the coevolution
of behavioral (web building), ecological (web microhabitat) and biomaterial (silk
biomechanics) traits that combined allow C. darwini to occupy a unique niche
among spiders.
PMID- 22046379
TI - Systems analysis of ATF3 in stress response and cancer reveals opposing effects
on pro-apoptotic genes in p53 pathway.
AB - Stress-inducible transcription factors play a pivotal role in cellular adaptation
to environment to maintain homeostasis and integrity of the genome. Activating
transcription factor 3 (ATF3) is induced by a variety of stress and inflammatory
conditions and is over-expressed in many kinds of cancer cells. However,
molecular mechanisms underlying pleiotropic functions of ATF3 have remained
elusive. Here we employed systems analysis to identify genome-wide targets of
ATF3 that is either induced by an alkylating agent methyl methanesulfonate (MMS)
or over-expressed in a prostate tumour cell line LNCaP. We show that stress
induced and cancer-associated ATF3 is recruited to 5,984 and 1,423 targets,
respectively, in the human genome, 89% of which are common. Notably, ATF3 targets
are highly enriched for not only ATF/CRE motifs but also binding sites of several
other stress-inducible transcription factors indicating an extensive network of
stress response factors in transcriptional regulation of target genes. Further
analysis of effects of ATF3 knockdown on these targets revealed that stress
induced ATF3 regulates genes in metabolic pathways, cell cycle, apoptosis, cell
adhesion, and signalling including insulin, p53, Wnt, and VEGF pathways. Cancer
associated ATF3 is involved in regulation of distinct sets of genes in processes
such as calcium signalling, Wnt, p53 and diabetes pathways. Notably, stress
induced ATF3 binds to 40% of p53 targets and activates pro-apoptotic genes such
as TNFRSF10B/DR5 and BBC3/PUMA. Cancer-associated ATF3, by contrast, represses
these pro-apoptotic genes in addition to CDKN1A/p21. Taken together, our data
reveal an extensive network of stress-inducible transcription factors and
demonstrate that ATF3 has opposing, cell context-dependent effects on p53 target
genes in DNA damage response and cancer development.
PMID- 22046380
TI - Changes in waist circumference and the incidence of acute myocardial infarction
in middle-aged men and women.
AB - BACKGROUND: Waist circumference (WC) measured at one point in time is positively
associated with the risk of acute myocardial infarction (MI), but the association
with changes in WC (DWC) is not clear. We investigated the association between
DWC and the risk of MI in middle-aged men and women, and evaluated the influence
from concurrent changes in BMI (DBMI). METHODOLOGY/PRINCIPAL FINDINGS: Data on
38,593 participants from the Danish Diet, Cancer and Health study was analysed.
Anthropometry was assessed in 1993-97 and 1999-02. Information on fatal and non
fatal MI was obtained from National Registers. Cases were validated by review of
the medical records. Hazard ratios (HR) were calculated from Cox proportional
hazard models with individuals considered at risk from 1999-02 until December 30
2009. During 8.4 years of follow-up, 1,041 incident cases of MI occurred. WC was
positively associated with the risk of MI, but weakly after adjustment for BMI.
DWC was not associated with the risk of MI (HR per 5 cm change = 1.01 (0.95,
1.09) with adjustment for covariates, baseline WC, BMI and DBMI). Associations
with DWC were not notably different in sub-groups stratified according to
baseline WC or DBMI, or when individuals with MI occurring within the first years
of follow-up were excluded. CONCLUSIONS/SIGNIFICANCE: WC was positively
associated with the risk of MI in middle-aged men and women, but changes in WC
were not. These findings suggest that a reduction in WC may be an insufficient
target for prevention of MI in middle-aged men and women.
PMID- 22046381
TI - Molecular evidence of the toxic effects of diatom diets on gene expression
patterns in copepods.
AB - BACKGROUND: Diatoms are dominant photosynthetic organisms in the world's oceans
and are considered essential in the transfer of energy through marine food
chains. However, these unicellular plants at times produce secondary metabolites
such as polyunsaturated aldehydes and other products deriving from the oxidation
of fatty acids that are collectively termed oxylipins. These cytotoxic compounds
are responsible for growth inhibition and teratogenic activity, potentially
sabotaging future generations of grazers by inducing poor recruitment in marine
organisms such as crustacean copepods. PRINCIPAL FINDINGS: Here we show that two
days of feeding on a strong oxylipin-producing diatom (Skeletonema marinoi) is
sufficient to inhibit a series of genes involved in aldehyde detoxification,
apoptosis, cytoskeleton structure and stress response in the copepod Calanus
helgolandicus. Of the 18 transcripts analyzed by RT-qPCR at least 50% were
strongly down-regulated (aldehyde dehydrogenase 9, 8 and 6, cellular apoptosis
susceptibility and inhibitor of apoptosis IAP proteins, heat shock protein 40,
alpha- and beta-tubulins) compared to animals fed on a weak oxylipin-producing
diet (Chaetoceros socialis) which showed no changes in gene expression profiles.
CONCLUSIONS: Our results provide molecular evidence of the toxic effects of
strong oxylipin-producing diatoms on grazers, showing that primary defense
systems that should be activated to protect copepods against toxic algae can be
inhibited. On the other hand other classical detoxification genes (glutathione S
transferase, superoxide dismutase, catalase, cytochrome P450) were not affected
possibly due to short exposure times. Given the importance of diatom blooms in
nutrient-rich aquatic environments these results offer a plausible explanation
for the inefficient use of a potentially valuable food resource, the spring
diatom bloom, by some copepod species.
PMID- 22046382
TI - Barriers to participation in a patient satisfaction survey: who are we missing?
AB - BACKGROUND: A common weakness of patient satisfaction surveys is a suboptimal
participation rate. Some patients may be unable to participate, because of
language barriers, physical limitations, or mental problems. As the role of these
barriers is poorly understood, we aimed to identify patient characteristics that
are associated with non-participation in a patient satisfaction survey.
METHODOLOGY: At the University Hospitals of Geneva, Switzerland, a patient
satisfaction survey is regularly conducted among all adult patients hospitalized
for >24 hours on a one-month period in the departments of internal medicine,
geriatrics, surgery, neurosciences, psychiatry, and gynaecology-obstetrics. In
order to assess the factors associated with non-participation to the patient
satisfaction survey, a case-control study was conducted among patients selected
for the 2005 survey. Cases (non respondents, n = 195) and controls (respondents,
n = 205) were randomly selected from the satisfaction survey, and information
about potential barriers to participation was abstracted in a blinded fashion
from the patients' medical and nursing charts. PRINCIPAL FINDINGS: Non
participation in the satisfaction survey was independently associated with the
presence of a language barrier (odds ratio [OR] 4.53, 95% confidence interval
[CI95%]: 2.14-9.59), substance abuse (OR 3.75, CI95%: 1.97-7.14), cognitive
limitations (OR 3.72, CI95%: 1.64-8.42), a psychiatric diagnosis (OR 1.99, CI95%:
1.23-3.23) and a sight deficiency (OR 2.07, CI95%: 0.98-4.36). The odds ratio for
non-participation increased gradually with the number of predictors. CONCLUSIONS:
Five barriers to non-participation in a mail survey were identified. Gathering
patient feedback through mailed surveys may lead to an under-representation of
some patient subgroups.
PMID- 22046383
TI - Distinct origin of the Y and St genome in Elymus species: evidence from the
analysis of a large sample of St genome species using two nuclear genes.
AB - BACKGROUND: Previous cytological and single copy nuclear genes data suggested the
St and Y genome in the StY-genomic Elymus species originated from different
donors: the St from a diploid species in Pseudoroegneria and the Y from an
unknown diploid species, which are now extinct or undiscovered. However, ITS data
suggested that the Y and St genome shared the same progenitor although rather few
St genome species were studied. In a recent analysis of many samples of St genome
species Pseudoroegneria spicata (Pursh) A. Love suggested that one accession of
P. spicata species was the most likely donor of the Y genome. The present study
tested whether intraspecific variation during sampling could affect the outcome
of analyses to determining the origin of Y genome in allotetraploid StY species.
We also explored the evolutionary dynamics of these species.
METHODOLOGY/PRINCIPAL FINDINGS: Two single copy nuclear genes, the second largest
subunit of RNA polymerase II (RPB2) and the translation elongation factor G (EF
G) sequences from 58 accessions of Pseudoroegneria and Elymus species, together
with those from Hordeum (H), Agropyron (P), Australopyrum (W), Lophopyrum (E(e)),
Thinopyrum (E(a)), Thinopyrum (E(b)), and Dasypyrum (V) were analyzed using
maximum parsimony, maximum likelihood and Bayesian methods. Sequence comparisons
among all these genomes revealed that the St and Y genomes are relatively
dissimilar. Extensive sequence variations have been detected not only between the
sequences from St and Y genome, but also among the sequences from diploid St
genome species. Phylogenetic analyses separated the Y sequences from the St
sequences. CONCLUSIONS/SIGNIFICANCE: Our results confirmed that St and Y genome
in Elymus species have originated from different donors, and demonstrated that
intraspecific variation does not affect the identification of genome origin in
polyploids. Moreover, sequence data showed evidence to support the suggestion of
the genome convergent evolution in allopolyploid StY genome species.
PMID- 22046384
TI - Multidimensional poverty and child survival in India.
AB - BACKGROUND: Though the concept of multidimensional poverty has been acknowledged
cutting across the disciplines (among economists, public health professionals,
development thinkers, social scientists, policy makers and international
organizations) and included in the development agenda, its measurement and
application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from
the National Family and Health Survey 3, India, this paper measures poverty in
multidimensional space and examine the linkages of multidimensional poverty with
child survival. The multidimensional poverty is measured in the dimension of
knowledge, health and wealth and the child survival is measured with respect to
infant mortality and under-five mortality. Descriptive statistics, principal
component analyses and the life table methods are used in the analyses. RESULTS:
The estimates of multidimensional poverty are robust and the inter-state
differentials are large. While infant mortality rate and under-five mortality
rate are disproportionately higher among the abject poor compared to the non
poor, there are no significant differences in child survival among educationally,
economically and health poor at the national level. State pattern in child
survival among the education, economical and health poor are mixed. CONCLUSION:
Use of multidimensional poverty measures help to identify abject poor who are
unlikely to come out of poverty trap. The child survival is significantly lower
among abject poor compared to moderate poor and non-poor. We urge to popularize
the concept of multiple deprivations in research and program so as to reduce
poverty and inequality in the population.
PMID- 22046385
TI - Loss of the alpha2beta1 integrin alters human papilloma virus-induced squamous
carcinoma progression in vivo and in vitro.
AB - Expression of the alpha2beta1 integrin, a receptor for collagens and laminin, is
altered during tumor progression. Recent studies have linked polymorphisms in the
alpha2 integrin gene with oral, squamous cell carcinoma (SCC). To determine the
alpha2beta1 integrin's role in SCC progression, we crossed alpha2-null mice with
K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was
evaluated in HPV-positive, alpha2-null (HPV/KO) and HPV-positive, wild-type
(HPV/WT) animals. alpha2beta1 integrin expression stimulated progression from
hyperplasia and papillomatosis to dysplasia with concomitant dermal mast cell
infiltration. Moreover, lymph node metastasis was decreased by 31.3% in HPV/KO,
compared to HPV/WT, animals. To evaluate the integrin-specific impact on the
malignant epithelium versus the microenvironment, we developed primary tumor cell
lines. Although transition from dysplasia to carcinoma was unaltered during
spontaneous tumor development, isolated primary HPV/KO SCC cell lines
demonstrated decreased migration and invasion, compared to HPV/WT cells. When
HPV/WT and HPV/KO SCC cells were orthotopically injected into WT or KO hosts,
tumor alpha2beta1 integrin expression resulted in decreased tumor latency,
regardless of host integrin status. HPV/WT SCC lines failed to demonstrate a
proliferative advantage in vitro, however, the HPV/WT tumors demonstrated
increased growth compared to HPV/KO SCC lines in vivo. Although contributions of
the integrin to the microenvironment cannot be excluded, our studies indicate
that alpha2beta1 integrin expression by HPV-transformed keratinocytes modulates
SCC growth and progression.
PMID- 22046386
TI - Evaluation of type-specific real-time PCR assays using the LightCycler and
J.B.A.I.D.S. for detection of adenoviruses in species HAdV-C.
AB - Sporadically, HAdVs from species HAdV-C are detected in acute respiratory disease
outbreaks. To rapidly type these viruses, we designed real-time PCR assays that
detect and discriminate between adenovirus types HAdV-C1, -C2, -C5, and -C6.
Sixteen clinical isolates from the California Department of Public Health were
used to validate the new assays. Type-specific TaqMan real-time PCR assays were
designed and used independently to successfully identify 16 representative
specimens. The lower limit of detection for our LightCycler singleplex real-time
PCR assays were calculated to be 100, 100, 100, and 50 genomic copies per
reaction for HAdV-C1, HAdV-C2, HAdV-C5 and HAdV-C6, respectively. The results for
the singleplex J.B.A.I.D.S. assays were similar. Our assays did not cross-react
with other adenoviruses outside of species HAdV-C, respiratory syncytial virus,
influenza, or respiratory disease causing bacteria. These assays have the
potential to be useful as diagnostic tools for species HAdV-C infection.
PMID- 22046387
TI - Behavioural correlate of choice confidence in a discrete trial paradigm.
AB - How animals make choices in a changing and often uncertain environment is a
central theme in the behavioural sciences. There is a substantial literature on
how animals make choices in various experimental paradigms but less is known
about the way they assess a choice after it has been made in terms of the
expected outcome. Here, we used a discrete trial paradigm to characterise how the
reward history shaped the behaviour on a trial by trial basis. Rats initiated
each trial which consisted of a choice between two drinking spouts that differed
in their probability of delivering a sucrose solution. Critically, sucrose was
delivered after a delay from the first lick at the spouts--this allowed us to
characterise the behavioural profile during the window between the time of choice
and its outcome. Rats' behaviour converged to optimum choice, both during the
acquisition phase and after the reversal of contingencies. We monitored the post
choice behaviour at a temporal precision of 1 millisecond; lick-response profiles
revealed that rats spent more time at the spout with the higher reward
probability and exhibited a sparser lick pattern. This was the case when we
exclusively examined the unrewarded trials, where the outcome was identical. The
differential licking profiles preceded the differential choice ratios and could
thus predict the changes in choice behaviour.
PMID- 22046388
TI - Urinary bisphenol A and type-2 diabetes in U.S. adults: data from NHANES 2003
2008.
AB - OBJECTIVE: Bisphenol A (BPA) is found in plastics and other consumer products;
exposure may lead to insulin resistance and development of type-2 diabetes
mellitus (T2DM) through over-activation of pancreatic beta-cells. Previous
studies using data from the National Health and Nutrition Examination Survey
(NHANES) showed an inconsistent association between prevalence of self-reported
T2DM and urinary BPA. We used a different diagnosis method of T2DM (hemoglobin
A1c (HbA1c)) with a larger subset of NHANES. METHODS AND FINDINGS: We analyzed
data from 4,389 adult participants who were part of a sub-study of environmental
phenol measurements in urine from three NHANES cycles from 2003 to 2008. T2DM was
defined as having a HbA1c >= 6.5% or use of diabetes medication. The weighted
prevalence of T2DM was 9.2%. Analysis of the total sample revealed that a two
fold increase in urinary BPA was associated with an odds ratio (OR) of 1.08 of
T2DM (95% confidence interval (CI), 1.02 to 1.16), after controlling for
potential confounders. However, when we examined each NHANES cycle individually,
we only found a statistically significant association in the 2003/04 cycle (n =
1,364, OR = 1.23 (95% CI, 1.07 to 1.42) for each doubling in urinary BPA). We
found no association in either the NHANES cycle from 2005/06 (n = 1,363, OR =
1.05 (95% CI, 0.94 to 1.18)); or 2007/08 (n = 1,662, OR = 1.06 (95% CI, 0.91 to
1.23)). Similar patterns of associations between BPA and continuous HbA1c were
also observed. CONCLUSIONS: Although higher urinary BPA was associated with
elevated HbA1c and T2DM in the pooled analysis, it was driven by data from only
one NHANES cycle. Additional studies, especially of a longitudinal design with
repeated BPA measurements, are needed to further elucidate the association
between BPA and T2DM.
PMID- 22046389
TI - Aerosolized human extracellular superoxide dismutase prevents hyperoxia-induced
lung injury.
AB - An important issue in critical care medicine is the identification of ways to
protect the lungs from oxygen toxicity and reduce systemic oxidative stress in
conditions requiring mechanical ventilation and high levels of oxygen. One way to
prevent oxygen toxicity is to augment antioxidant enzyme activity in the
respiratory system. The current study investigated the ability of aerosolized
extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic
injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic
cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1
mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic
effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system
for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia
were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo
2'-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to
hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased
significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung
and liver were significantly decreased on day 2 (P<0.01) but the marker in the
liver increased abruptly after day 3 of hyperoxia when the mortality increased.
Treatment with aerosolized rhEC-SOD increased the survival rate at day 3 under
hyperoxia to 95.8%, which was significantly higher than that of the control group
(57.1%), albumin treated group (33.3%), and CuZn-SOD treated group (75%). The
protective effects of EC-SOD against hyperoxia were further confirmed by reduced
lung edema and systemic oxidative stress. Aerosolized EC-SOD protected mice
against oxygen toxicity and reduced mortality in a hyperoxic model. The results
encourage the use of an aerosol therapy with EC-SOD in intensive care units to
reduce oxidative injury in patients with severe hypoxemic respiratory failure,
including acute respiratory distress syndrome (ARDS).
PMID- 22046390
TI - Evolutionary consequences of altered atmospheric oxygen in Drosophila
melanogaster.
AB - Twelve replicate populations of Drosophila melanogaster, all derived from a
common ancestor, were independently evolved for 34+ generations in one of three
treatment environments of varying PO(2): hypoxia (5.0-10.1 kPa), normoxia (21.3
kPa), and hyperoxia (40.5 kPa). Several traits related to whole animal
performance and metabolism were assayed at various stages via "common garden" and
reciprocal transplant assays to directly compare evolved and acclimatory
differences among treatments. Results clearly demonstrate the evolution of a
greater tolerance to acute hypoxia in the hypoxia-evolved populations, consistent
with adaptation to this environment. Greater hypoxia tolerance was associated
with an increase in citrate synthase activity in fly homogenate when compared to
normoxic (control) populations, suggesting an increase in mitochondrial volume
density in these populations. In contrast, no direct evidence of increased
performance of the hyperoxia-evolved populations was detected, although a
significant decrease in the tolerance of these populations to acute hypoxia
suggests a cost to adaptation to hyperoxia. Hyperoxia-evolved populations had
lower productivity overall (i.e., across treatment environments) and there was no
evidence that hypoxia or hyperoxia-evolved populations had greatest productivity
or longevity in their respective treatment environments, suggesting that these
assays failed to capture the components of fitness relevant to adaptation.
PMID- 22046391
TI - Population attributable risk of unintentional childhood poisoning in Karachi
Pakistan.
AB - BACKGROUND: The percentage of unintentional childhood poisoning cases in a given
population attributable to specific risk factors (i.e., the population
attributable risk) which can be calculated; determination of such risk factors
associated with potentially modifiable risk factors, are necessary to focus on
the prevention strategies. METHODS: We calculated PARs, using 120 cases with
unintentional poisoning and 360 controls in a hospital based matched case-
control study. The risk factors were accessibility to hazardous chemicals and
medicines due to unsafe storage, child behavior reported as hyperactive, storage
of kerosene and petroleum in soft drink bottles, low socioeconomic class, less
education of the mother and the history of previous poisoning. RESULTS: THE
FOLLOWING ATTRIBUTED RISKS WERE OBSERVED: 12% (95% confidence interval [CI] = 8%
16%) for both chemicals and medicines stored unsafe, 19% (15%-23%) for child
reported as hyperactive, 40% (38%-42%) for storage of kerosene and petroleum in
soft drink bottles, 48% (42%-54%) for low socioeconomic status, 38% (32%-42%) for
no formal mothers education and 5.8% (2%-10%) for history of previous poisoning.
48% of cases for overall study population which could be attributed to at least
one of the six risk factors. Among girls, this proportion was 23% and 43% among
boys. About half of the unintentional childhood poisoning cases in this Pakistani
population could be avoided. CONCLUSION: Exposure to potentially modifiable risk
indicators explained about half of the cases of unintentional poisoning among
children under five years of age in this Pakistani population, indicating the
theoretical scope for prevention of the disease.
PMID- 22046393
TI - Tissue-restricted expression of Nrf2 and its target genes in zebrafish with gene
specific variations in the induction profiles.
AB - The Keap1-Nrf2 system serves as a defense mechanism against oxidative stress and
electrophilic toxicants by inducing more than one hundred cytoprotective
proteins, including antioxidants and phase 2 detoxifying enzymes. Since induction
profiles of Nrf2 target genes have been studied exclusively in cultured cells,
and not in animal models, their tissue-specificity has not been well
characterized. In this paper, we examined and compared the tissue-specific
expression of several Nrf2 target genes in zebrafish larvae by whole-mount in
situ hybridization (WISH). Seven zebrafish genes (gstp1, mgst3b, prdx1, frrs1c,
fthl, gclc and hmox1a) suitable for WISH analysis were selected from candidates
for Nrf2 targets identified by microarray analysis. Tissue-restricted induction
was observed in the nose, gill, and/or liver for all seven genes in response to
Nrf2-activating compounds, diethylmaleate (DEM) and sulforaphane. The Nrf2 gene
itself was dominantly expressed in these three tissues, implying that tissue
restricted induction of Nrf2 target genes is defined by tissue-specific
expression of Nrf2. Interestingly, the induction of frrs1c and gclc in liver and
nose, respectively, was quite low and that of hmox1a was restricted in the liver.
These results indicate the existence of gene-specific variations in the tissue
specificity, which can be controlled by factors other than Nrf2.
PMID- 22046392
TI - Screening for active small molecules in mitochondrial complex I deficient
patient's fibroblasts, reveals AICAR as the most beneficial compound.
AB - Congenital deficiency of the mitochondrial respiratory chain complex I (CI) is a
common defect of oxidative phosphorylation (OXPHOS). Despite major advances in
the biochemical and molecular diagnostics and the deciphering of CI structure,
function assembly and pathomechanism, there is currently no satisfactory cure for
patients with mitochondrial complex I defects. Small molecules provide one
feasible therapeutic option, however their use has not been systematically
evaluated using a standardized experimental system. In order to evaluate
potentially therapeutic compounds, we set up a relatively simple system measuring
different parameters using only a small amount of patient's fibroblasts, in
glucose free medium, where growth is highly OXPOS dependent. Ten different
compounds were screened using fibroblasts derived from seven CI patients,
harboring different mutations.5-Aminoimidazole-4-carboxamide ribotide (AICAR) was
found to be the most beneficial compound improving growth and ATP content while
decreasing ROS production. AICAR also increased mitochondrial biogenesis without
altering mitochondrial membrane potential (Deltapsi). Fluorescence microscopy
data supported increased mitochondrial biogenesis and activation of the AMP
activated protein kinase (AMPK). Other compounds such as; bezafibrate and
oltipraz were rated as favorable while polyphenolic phytochemicals (resverastrol,
grape seed extract, genistein and epigallocatechin gallate) were found not
significant or detrimental. Although the results have to be verified by more
thorough investigation of additional OXPHOS parameters, preliminary rapid
screening of potential therapeutic compounds in individual patient's fibroblasts
could direct and advance personalized medical treatment.
PMID- 22046394
TI - Predictors of limb fat gain in HIV positive patients following a change to
tenofovir-emtricitabine or abacavir-lamivudine.
AB - BACKGROUND: Antiretroviral treatment (cART) in HIV causes lipoatrophy. We
examined predictors of anthropometric outcomes over 96 weeks in HIV-infected,
lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine
(TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations.
METHODOLOGY/PRINCIPAL FINDINGS: The STEAL study was a prospective trial of
virologically suppressed participants randomised to either TDF-FTC (n = 178) or
ABC-3TC (n = 179). Anthropometric assessment was conducted at baseline, weeks 48
and 96. The analysis population included those with baseline and week 96 data
remaining on randomised therapy. Distribution of limb fat change was divided into
four categories (<= 0%, >0-10%, >10-20%, >20%). Baseline characteristics
[demographics, medical history, metabolic and cardiovascular biomarkers] were
assessed as potential predictors of change in percent subcutaneous limb fat using
linear regression. 303 participants (85% of STEAL population) were included.
Baseline characteristics were: mean (+/- SD) age 45 (+/- 8) years; thymidine
analogue nucleoside reverse transcriptase inhibitor (tNRTI) duration 4 (+/- 3)
years; limb fat 5.4 (+/- 3.0)kg; body mass index 24.7 (+/- 3 .5) kg/m(2). Mean
(SD) limb fat gain to week 48 and 96 was 7.6% (+/- 22.4) and 13.2% (+/- 27.3),
respectively, with no significant difference between groups. 51.5% of all
participants had >10% gain in limb fat. Predictors of greater limb fat gain at
week 96 were baseline tNRTI (10.3, p = 0.001), glucose >6 mmol/L (16.1, p =
0.04), higher interleukin 6 (IL-6) (2.8, p = 0.004) and lower baseline limb fat
(3.8-6.4 kg - 11.2; >6.4 kg - 15.7, p trend<0.001). CONCLUSIONS/SIGNIFICANCE:
Modest peripheral fat gain occurred with both TDF-FTC and ABC-3TC. Baseline
factors associated with more severe lipodystrophy (lipoatrophy, baseline tNRTI,
raised IL6, and glucose) predicted greater limb fat recovery at 96 weeks.
PMID- 22046395
TI - Venom of parasitoid, Pteromalus puparum, suppresses host, Pieris rapae, immune
promotion by decreasing host C-type lectin gene expression.
AB - BACKGROUND: Insect hosts have evolved immunity against invasion by parasitoids,
and in co-evolutionary response parasitoids have also developed strategies to
overcome host immune systems. The mechanisms through which parasitoid venoms
disrupt the promotion of host immunity are still unclear. We report here a new
mechanism evolved by parasitoid Pteromalus puparum, whose venom inhibited the
promotion of immunity in its host Pieris rapae (cabbage white butterfly).
METHODOLOGY/PRINCIPAL FINDINGS: A full-length cDNA encoding a C-type lectin (Pr
CTL) was isolated from P. rapae. Quantitative PCR and immunoblotting showed that
injection of bacterial and inert beads induced expression of Pr-CTL, with peaks
of mRNA and Pr-CTL protein levels at 4 and 8 h post beads challenge,
respectively. In contrast, parasitoid venom suppressed Pr-CTL expression when co
injected with beads, in a time and dose-dependent manner. Immunolocalization and
immunoblotting results showed that Pr-CTL was first detectable in vesicles
present in cytoplasm of granulocytes in host hemolymph, and was then secreted
from cells into circulatory fluid. Finally, the secreted Pr-CTL bound to cellular
membranes of both granulocytes and plasmatocytes. Injection of double-stranded
RNA specific for target gene decreased expression of Pr-CTL, and a few other host
immune-related genes. Suppression of Pr-CTL expression also down-regulated
antimicrobial and phenoloxidase activities, and reducing phagocytotic and
encapsulation rates in host. The inhibitory effect of parasitoid venom on host
encapsulation is consistent with its effect in suppressing Pr-CTL expression.
Binding assay results showed that recombinant Pr-CTL directly attached to the
surface of P. puparum egges. We infer that Pr-CTL may serve as an immune
signalling co-effector, first binding to parasitoid eggs, regulating expression
of a set of immune-related genes and promoting host immunity.
CONCLUSIONS/SIGNIFICANCE: P. puparum venom inhibits promotion of host immune
responses by silencing expression of host C-type lectin gene Pr-CTL, whose
expression affected transcription of other host immune-related genes.
PMID- 22046396
TI - High-throughput analysis of calcium signalling kinetics in astrocytes stimulated
with different neurotransmitters.
AB - Astrocytes express a wide range of receptors for neurotransmitters and hormones
that are coupled to increases in intracellular Ca(2+) concentration, enabling
them to detect activity in both neuronal and vascular networks. There is
increasing evidence that astrocytes are able to discriminate between different
Ca(2+)-linked stimuli, as the efficiency of some Ca(2+) dependent processes-
notably release of gliotransmitters--depends on the stimulus that initiates the
Ca(2+) signal. The spatiotemporal complexity of Ca(2+) signals is substantial,
and we here tested the hypothesis that variation in the kinetics of Ca(2+)
responses could offer a means of selectively engaging downstream targets, if
agonists exhibited a "signature shape" in evoked Ca(2+) response. To test this,
astrocytes were exposed to three different receptor agonists (ATP, glutamate and
histamine) and the resultant Ca(2+) signals were analysed for systematic
differences in kinetics that depended on the initiating stimulus. We found
substantial heterogeneity between cells in the time course of Ca(2+) responses,
but the variation did not correlate with the type or concentration of the
stimulus. Using a simple metric to quantify the extent of difference between
populations, it was found that the variation between agonists was insufficient to
allow signal discrimination. We conclude that the time course of global
intracellular Ca(2+) signals does not offer the cells a means for distinguishing
between different neurotransmitters.
PMID- 22046397
TI - Validity of verbal autopsy procedures for determining malaria deaths in different
epidemiological settings in Uganda.
AB - BACKGROUND: Verbal autopsy (VA) procedures can be used to estimate cause of death
in settings with inadequate vital registries. However, the sensitivity of VA for
determining malaria-specific mortality may be low, and may vary with transmission
intensity. We assessed the diagnostic accuracy of VA procedures as compared to
hospital medical records for determining cause of death in children under five in
three different malaria transmission settings in Uganda, including Tororo (high),
Kampala (medium), and Kisoro (low). METHODS AND FINDINGS: Caretakers of children
who died in participating hospitals were interviewed using a standardized World
Health Organization questionnaire. Medical records from the child's
hospitalization were also reviewed. Causes of death based on the VA
questionnaires and the medical records were assigned independently by physician
reviewers and then compared. A total of 719 cases were included in the final
analysis, 67 in Tororo, 600 in Kampala, and 52 in Kisoro. Malaria was classified
as the underlying or contributory cause of death by review of medical records in
33 deaths in Tororo, 60 in Kampala, and 0 in Kisoro. The sensitivity of VA
procedures for determining malaria deaths in Tororo was 61% (95% CI 44-78%) and
50% in Kampala (95% CI 37-63%). Specificity for determining malaria deaths in
Tororo and Kampala was high (>88%), but positive predictive value varied widely,
from 83% in Tororo to 34% in Kampala (difference 49%, 95% CI 31-67, p<0.001). The
difference between the cause-specific mortality fraction for malaria as
determined by VA procedures and medical records was -11% in Tororo, +5% in
Kampala, and +14% in Kisoro. CONCLUSIONS: Our results suggest that these VA
methods have an acceptable level of diagnostic accuracy for determining malaria
deaths at the population level in high and medium transmission areas, but not in
low transmission areas.
PMID- 22046398
TI - Grooming coercion and the post-conflict trading of social services in wild
Barbary macaques.
AB - In animal and human societies, social services such as protection from predators
are often exchanged between group members. The tactics that individuals display
to obtain a service depend on its value and on differences between individuals in
their capacity to aggressively obtain it. Here we analysed the exchange of
valuable social services (i.e. grooming and relationship repair) in the aftermath
of a conflict, in wild Barbary macaques (Macaca sylvanus). The relationship
repair function of post-conflict affiliation (i.e. reconciliation) was apparent
in the victim but not in the aggressor. Conversely, we found evidence for
grooming coercion by the aggressor; when the victim failed to give grooming soon
after a conflict they received renewed aggression from the aggressor. We argue
that post-conflict affiliation between former opponents can be better described
as a trading of social services rather than coercion alone, as both animals
obtain some benefits (i.e. grooming for the aggressor and relationship repair for
the victim). Our study is the first to test the importance of social coercion in
the aftermath of a conflict. Differences in competitive abilities can affect the
exchange of services and the occurrence of social coercion in animal societies.
This may also help explain the variance between populations and species in their
social behaviour and conflict management strategies.
PMID- 22046399
TI - Lrp acts as both a positive and negative regulator for type 1 fimbriae production
in Salmonella enterica serovar Typhimurium.
AB - Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator
of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via
direct regulation of FimZ, a direct positive regulator for type 1 fimbriae
production. Using RT-PCR, we have shown previously that fimA transcription is
dramatically impaired in both lrp-deletion (Deltalrp) and constitutive-lrp
expression (lrp(C)) mutant strains. In this work, we used chromosomal P(fimA)
lacZ fusions and yeast agglutination assays to confirm and extend our previous
results. Direct binding of Lrp to P(fimA) was shown by an electrophoretic
mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis
revealed that the Lrp-binding motifs in P(fimA) play a role in both activation
and repression of type 1 fimbriae production. Overproduction of Lrp also
abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins
independently bind to P(fimA) without competitive exclusion. In addition, both
Lrp and FimZ binding to P(fimA) caused a hyper retardation (supershift) of the
DNA-protein complex compared to the shift when each protein was present alone.
Nutrition-dependent cellular Lrp levels closely correlated with the amount of
type 1 fimbriae production. These observations suggest that Lrp plays important
roles in type 1 fimbriation by acting as both a positive and negative regulator
and its effect depends, at least in part, on the cellular concentration of Lrp in
response to the nutritional environment.
PMID- 22046400
TI - Modulation ofTcf7l2 expression alters behavior in mice.
AB - The comorbidity of type 2 diabetes (T2D) with several psychiatric diseases is
well established. While environmental factors may partially account for these co
occurrences, common genetic susceptibilities could also be implicated in the
confluence of these diseases. In support of shared genetic burdens, TCF7L2, the
strongest genetic determinant for T2D risk in the human population, has been
recently implicated in schizophrenia (SCZ) risk, suggesting that this may be one
of many loci that pleiotropically influence both diseases. To investigate whether
Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose
metabolism, we conducted several behavioral tests in mice with null alleles of
Tcf7l2 or overexpressing Tcf7l2. We identified a role for Tcf7l2 in anxiety-like
behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of
the mutant mice showed differences in prepulse inhibition (PPI), which is a well
established endophenotype for SCZ. These results show that Tcf7l2 alters behavior
in mice. Importantly, these differences are observed prior to the onset of
detectable glucose metabolism abnormalities. Whether these differences are
related to human anxiety-disorders or schizophrenia remains to be determined.
These animal models have the potential to elucidate the molecular basis of
psychiatric comorbidities in diabetes and should therefore be studied further.
PMID- 22046401
TI - Fatty-acid preference changes during development in Drosophila melanogaster.
AB - Fatty-acids (FAs) are required in the diet of many animals throughout their life.
However, the mechanisms involved in the perception of and preferences for dietary
saturated and unsaturated FAs (SFAs and UFAs, respectively) remain poorly
explored, especially in insects. Using the model species Drosophila melanogaster,
we measured the responses of wild-type larvae and adults to pure SFAs (14, 16,
and 18 carbons) and UFAs (C18 with 1, 2, or 3 double-bonds). Individual and group
behavioral tests revealed different preferences in larvae and adults. Larvae
preferred UFAs whereas SFAs tended to induce both a strong aversion and a
persistent aggregation behavior. Adults generally preferred SFAs, and laid more
eggs and had a longer life span when ingesting these substances as compared to
UFAs. Our data suggest that insects can discriminate long-chain dietary FAs. The
developmental change in preference shown by this species might reflect functional
variation in use of FAs or stage-specific nutritional requirements, and may be
fundamental for insect use of these major dietary components.
PMID- 22046402
TI - Methanosarcina acetivorans C2A topoisomerase IIIalpha, an archaeal enzyme with
promiscuity in divalent cation dependence.
AB - Topoisomerases play a fundamental role in genome stability, DNA replication and
repair. As a result, topoisomerases have served as therapeutic targets of
interest in Eukarya and Bacteria, two of the three domains of life. Since members
of Archaea, the third domain of life, have not been implicated in any diseased
state to-date, there is a paucity of data on archaeal topoisomerases. Here we
report Methanosarcina acetivorans TopoIIIalpha (MacTopoIIIalpha) as the first
biochemically characterized mesophilic archaeal topoisomerase. Maximal activity
for MacTopoIIIalpha was elicited at 30-35 degrees C and 100 mM NaCl. As little as
10 fmol of the enzyme initiated DNA relaxation, and NaCl concentrations above 250
mM inhibited this activity. The present study also provides the first evidence
that a type IA Topoisomerase has activity in the presence of all divalent cations
tested (Mg(2+), Ca(2+), Sr(2+), Ba(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+),
Zn(2+) and Cd(2+)). Activity profiles were, however, specific to each metal.
Known type I (ssDNA and camptothecin) and type II (etoposide, novobiocin and
nalidixic acid) inhibitors with different mechanisms of action were used to
demonstrate that MacTopoIIIalpha is a type IA topoisomerase. Alignment of
MacTopoIIIalpha with characterized topoisomerases identified Y317 as the putative
catalytic residue, and a Y317F mutation ablated DNA relaxation activity,
demonstrating that Y317 is essential for catalysis. As the role of Domain V (C
terminal domain) is unclear, MacTopoIIIalpha was aligned with the canonical E.
coli TopoI 67 kDa fragment in order to construct an N-terminal (1-586) and a C
terminal (587-752) fragment for analysis. Activity could neither be elicited from
the fragments individually nor reconstituted from a mixture of the fragments,
suggesting that native folding is impaired when the two fragments are expressed
separately. Evidence that each of the split domains plays a role in Zn(2+)
binding of the enzyme is also provided.
PMID- 22046403
TI - Investigation of variation in gene expression profiling of human blood by
extended principle component analysis.
AB - BACKGROUND: Human peripheral blood is a promising material for biomedical
research. However, various kinds of biological and technological factors result
in a large degree of variation in blood gene expression profiles.
METHODOLOGY/PRINCIPAL FINDINGS: Human peripheral blood samples were drawn from
healthy volunteers and analysed using the Human Genome U133Plus2 Microarray. We
applied a novel approach using the Principle Component Analysis and Eigen-R(2)
methods to dissect the overall variation of blood gene expression profiles with
respect to the interested biological and technological factors. The results
indicated that the predominating sources of the variation could be traced to the
individual heterogeneity of the relative proportions of different blood cell
types (leukocyte subsets and erythrocytes). The physiological factors like age,
gender and BMI were demonstrated to be associated with 5.3% to 9.2% of the total
variation in the blood gene expression profiles. We investigated the gene
expression profiles of samples from the same donors but with different levels of
RNA quality. Although the proportion of variation associated to the RNA Integrity
Number was mild (2.1%), the significant impact of RNA quality on the expression
of individual genes was observed. CONCLUSIONS: By characterizing the major
sources of variation in blood gene expression profiles, such variability can be
minimized by modifications to study designs. Increasing sample size, balancing
confounding factors between study groups, using rigorous selection criteria for
sample quality, and well controlled experimental processes will significantly
improve the accuracy and reproducibility of blood transcriptome study.
PMID- 22046404
TI - Rates of mutation and host transmission for an Escherichia coli clone over 3
years.
AB - Although over 50 complete Escherichia coli/Shigella genome sequences are
available, it is only for closely related strains, for example the O55:H7 and
O157:H7 clones of E. coli, that we can assign differences to individual
evolutionary events along specific lineages. Here we sequence the genomes of 14
isolates of a uropathogenic E. coli clone that persisted for 3 years within a
household, including a dog, causing a urinary tract infection (UTI) in the dog
after 2 years. The 20 mutations observed fit a single tree that allows us to
estimate the mutation rate to be about 1.1 per genome per year, with minimal
evidence for adaptive change, including in relation to the UTI episode. The host
data also imply at least 6 host transfer events over the 3 years, with 2 lineages
present over much of that period. To our knowledge, these are the first direct
measurements for a clone in a well-defined host community that includes rates of
mutation and host transmission. There is a concentration of non-synonymous
mutations associated with 2 transfers to the dog, suggesting some selection
pressure from the change of host. However, there are no changes to which we can
attribute the UTI event in the dog, which suggests that this occurrence after 2
years of the clone being in the household may have been due to chance, or some
unknown change in the host or environment. The ability of a UTI strain to persist
for 2 years and also to transfer readily within a household has implications for
epidemiology, diagnosis, and clinical intervention.
PMID- 22046405
TI - The interaction between the first transmembrane domain and the thumb of ASIC1a is
critical for its N-glycosylation and trafficking.
AB - Acid-sensing ion channel-1a (ASIC1a), the primary proton receptor in the brain,
contributes to multiple diseases including stroke, epilepsy and multiple
sclerosis. Thus, a better understanding of its biogenesis will provide important
insights into the regulation of ASIC1a in diseases. Interestingly, ASIC1a
contains a large, yet well organized ectodomain, which suggests the hypothesis
that correct formation of domain-domain interactions at the extracellular side is
a key regulatory step for ASIC1a maturation and trafficking. We tested this
hypothesis here by focusing on the interaction between the first transmembrane
domain (TM1) and the thumb of ASIC1a, an interaction known to be critical in
channel gating. We mutated Tyr71 and Trp287, two key residues involved in the TM1
thumb interaction in mouse ASIC1a, and found that both Y71G and W287G decreased
synaptic targeting and surface expression of ASIC1a. These defects were likely
due to altered folding; both mutants showed increased resistance to tryptic
cleavage, suggesting a change in conformation. Moreover, both mutants lacked the
maturation of N-linked glycans through mid to late Golgi. These data suggest that
disrupting the interaction between TM1 and thumb alters ASIC1a folding, impedes
its glycosylation and reduces its trafficking. Moreover, reducing the culture
temperature, an approach commonly used to facilitate protein folding, increased
ASIC1a glycosylation, surface expression, current density and slowed the rate of
desensitization. These results suggest that correct folding of extracellular
ectodomain plays a critical role in ASIC1a biogenesis and function.
PMID- 22046406
TI - Association of new loci identified in European genome-wide association studies
with susceptibility to type 2 diabetes in the Japanese.
AB - BACKGROUND: Several novel susceptibility loci for type 2 diabetes have been
identified through genome-wide association studies (GWAS) for type 2 diabetes or
quantitative traits related to glucose metabolism in European populations. To
investigate the association of the 13 new European GWAS-derived susceptibility
loci with type 2 diabetes in the Japanese population, we conducted a replication
study using 3 independent Japanese case-control studies. METHODOLOGY/PRINCIPAL
FINDINGS: We examined the association of single nucleotide polymorphisms (SNPs)
within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1,
CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants
(2,839 cases and 2,125 controls) from 3 independent Japanese samples. The
association of each SNP with type 2 diabetes was analyzed by logistic regression
analysis. Further, we performed combined meta-analyses for the 3 studies and
previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The
meta-analysis revealed that rs2943641 in the IRS1 locus was significantly
associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval;
1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14
locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2
diabetes in the present Japanese samples (P<0.05). CONCLUSIONS: These results
indicate that IRS1 locus may be common locus for type 2 diabetes across different
ethnicities.
PMID- 22046407
TI - Thymosin beta 4 prevents oxidative stress by targeting antioxidant and anti
apoptotic genes in cardiac fibroblasts.
AB - RATIONALE: Thymosin beta-4 (Tbeta4) is a ubiquitous protein with diverse
functions relating to cell proliferation and differentiation that promotes wound
healing and modulates inflammatory responses. The effecter molecules targeted by
Tbeta4 for cardiac protection remains unknown. The purpose of this study is to
determine the molecules targeted by Tbeta4 that mediate cardio-protection under
oxidative stress. METHODS: Rat neonatal fibroblasts cells were exposed to
hydrogen peroxide (H(2)O(2)) in presence and absence of Tbeta4 and expression of
antioxidant, apoptotic and pro-fibrotic genes was evaluated by quantitative real
time PCR and western blotting. Reactive oxygen species (ROS) levels were
estimated by DCF-DA using fluorescent microscopy and fluorimetry. Selected
antioxidant and antiapoptotic genes were silenced by siRNA transfections in
cardiac fibroblasts and the effect of Tbeta4 on H(2)O(2)-induced profibrotic
events was evaluated. RESULTS: Pre-treatment with Tbeta4 resulted in reduction of
the intracellular ROS levels induced by H(2)O(2) in the cardiac fibroblasts. This
was associated with an increased expression of antioxidant enzymes Cu/Zn
superoxide dismutase (SOD) and catalase and reduction of Bax/Bcl(2) ratio. Tbeta4
treatment reduced the expression of pro-fibrotic genes [connective tissue growth
factor (CTGF), collagen type-1 (Col-I) and collagen type-3 (Col-III)] in the
cardiac fibroblasts. Silencing of Cu/Zn-SOD and catalase gene triggered apoptotic
cell death in the cardiac fibroblasts, which was prevented by treatment with
Tbeta4. CONCLUSION: This is the first report that exhibits the targeted molecules
modulated by Tbeta4 under oxidative stress utilizing the cardiac fibroblasts.
Tbeta4 treatment prevented the profibrotic gene expression in the in vitro
settings. Our findings indicate that Tbeta4 selectively targets and upregulates
catalase, Cu/Zn-SOD and Bcl(2), thereby, preventing H(2)O(2)-induced profibrotic
changes in the myocardium. Further studies are warranted to elucidate the
signaling pathways involved in the cardio-protection afforded by Tbeta4.
PMID- 22046408
TI - Development of gene expression markers of acute heat-light stress in reef
building corals of the genus Porites.
AB - Coral reefs are declining worldwide due to increased incidence of climate-induced
coral bleaching, which will have widespread biodiversity and economic impacts. A
simple method to measure the sub-bleaching level of heat-light stress experienced
by corals would greatly inform reef management practices by making it possible to
assess the distribution of bleaching risks among individual reef sites. Gene
expression analysis based on quantitative PCR (qPCR) can be used as a diagnostic
tool to determine coral condition in situ. We evaluated the expression of 13
candidate genes during heat-light stress in a common Caribbean coral Porites
astreoides, and observed strong and consistent changes in gene expression in two
independent experiments. Furthermore, we found that the apparent return to
baseline expression levels during a recovery phase was rapid, despite visible
signs of colony bleaching. We show that the response to acute heat-light stress
in P. astreoides can be monitored by measuring the difference in expression of
only two genes: Hsp16 and actin. We demonstrate that this assay discriminates
between corals sampled from two field sites experiencing different temperatures.
We also show that the assay is applicable to an Indo-Pacific congener, P. lobata,
and therefore could potentially be used to diagnose acute heat-light stress on
coral reefs worldwide.
PMID- 22046409
TI - Clinical symptoms in fibromyalgia are better associated to lipid peroxidation
levels in blood mononuclear cells rather than in plasma.
AB - BACKGROUND: We examined lipid peroxidation (LPO) in blood mononuclear cells
(BMCs) and plasma, as a marker of oxidative damage, and its association to
clinical symptoms in Fibromyalgia (FM) patients. METHODS: We conducted a case
control and correlational study comparing 65 patients and 45 healthy controls.
Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire
(FIQ), visual analogues scales (VAS), and the Beck Depression Inventory (BDI).
Oxidative stress was determined by measuring LPO in BMCs and plasma. RESULTS: We
found increased LPO levels in BMCs and plasma from FM patients as compared to
normal control (P<0.001). A significant correlation between LPO in BMCs and
clinical parameters was observed (r = 0.584, P<0.001 for VAS; r = 0.823, P<0.001
for FIQ total score; and r = 0.875, P<0.01 for depression in the BDI). We also
found a positive correlation between LPO in plasma and clinical symptoms (r =
0.452, P<0.001 for VAS; r = 0.578, P<0.001 for FIQ total score; and r = 0.579,
P<0.001 for depression in the BDI). Partial correlation analysis controlling for
age and BMI, and sex, showed that both LPO in cells and plasma were independently
associated to clinical symptoms. However, LPO in cells, but not LPO in plasma,
was independently associated to clinical symptoms when controlling for depression
(BDI scores). DISCUSSION: The results of this study suggest a role for oxidative
stress in the pathophysiology of fibromyalgia and that LPO in BMCs rather than
LPO in plasma is better associated to clinical symptoms in FM.
PMID- 22046410
TI - c-Kit-mediated functional positioning of stem cells to their niches is essential
for maintenance and regeneration of adult hematopoiesis.
AB - The mechanism by which hematopoietic stem and progenitor cells (HSPCs) through
interaction with their niches maintain and reconstitute adult hematopoietic cells
is unknown. To functionally and genetically track localization of HSPCs with
their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase
technology to conditionally delete c-Kit in adult mice, while simultaneously
enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c
Kit resulted in hematopoietic failure and splenic atrophy both at steady state
and after marrow ablation leading to the demise of the treated adult mice. Within
the marrow, the c-Kit-expressing GFP(+) cells were positioned to Kit ligand (KL)
expressing niche cells. This c-Kit-mediated cellular adhesion was essential for
long-term maintenance and expansion of HSPCs. These results lay the foundation
for delivering KL within specific niches to maintain and restore hematopoiesis.
PMID- 22046411
TI - Variation in cooperative behaviour within a single city.
AB - Human cooperative behaviour, as assayed by decisions in experimental economic
dilemmas such as the Dictator Game, is variable across human populations. Within
population variation has been less well studied, especially within industrial
societies. Moreover, little is known about the extent to which community-level
variation in Dictator Game behaviour relates to community-level variation in real
world social behaviour. We chose two neighbourhoods of the city of Newcastle upon
Tyne that were similar in most regards, but at opposite ends of the spectrum in
terms of level of socioeconomic deprivation. We administered Dictator Games to
randomly-selected residents, and also gathered a large number of more
naturalistic measures of cooperativeness. There were dramatic differences in
Dictator Game behaviour between the two neighbourhoods, with the mean allocation
to the other player close to half the stake in the affluent neighbourhood, and
close to one tenth of the stake in the deprived neighbourhood. Moreover, the
deprived neighbourhood was also characterised by lower self-reported social
capital, higher frequencies of crime and antisocial behaviour, a higher frequency
of littering, and less willingness to take part in a survey or return a lost
letter. On the other hand, there were no differences between the neighbourhoods
in terms of the probability of helping a person who dropped an object, needed
directions to a hospital, or needed to make change for a coin, and people on the
streets were less likely to be alone in the deprived neighbourhood than the
affluent one. We conclude that there can be dramatic local differences in
cooperative behaviour within the same city, and that these need further
theoretical explanation.
PMID- 22046412
TI - Novel sex cells and evidence for sex pheromones in diatoms.
AB - BACKGROUND: Diatoms belong to the stramenopiles, one of the largest groups of
eukaryotes, which are primarily characterized by a presence of an anterior
flagellum with tubular mastigonemes and usually a second, smooth flagellum. Based
on cell wall morphology, diatoms have historically been divided into centrics and
pennates, of which only the former have flagella and only on the sperm. Molecular
phylogenies show the pennates to have evolved from among the centrics. However,
the timing of flagellum loss--whether before the evolution of the pennate lineage
or after--is unknown, because sexual reproduction has been so little studied in
the 'araphid' basal pennate lineages, to which Pseudostaurosira belongs.
METHODS/PRINCIPAL FINDING: Sexual reproduction of an araphid pennate,
Pseudostaurosira trainorii, was studied with light microscopy (including time
lapse observations and immunofluorescence staining observed under confocal
scanning laser microscopy) and SEM. We show that the species produces motile male
gametes. Motility is mostly associated with the extrusion and retrieval of
microtubule-based 'threads', which are structures hitherto unknown in
stramenopiles, their number varying from one to three per cell. We also report
experimental evidence for sex pheromones that reciprocally stimulate
sexualization of compatible clones and orientate motility of the male gametes
after an initial 'random walk'. CONCLUSIONS/SIGNIFICANCE: The threads
superficially resemble flagella, in that both are produced by male gametes and
contain microtubules. However, one striking difference is that threads cannot
beat or undulate and have no motility of their own, and they do not bear
mastigonemes. Threads are sticky and catch and draw objects, including eggs. The
motility conferred by the threads is probably crucial for sexual reproduction of
P. trainorii, because this diatom is non-motile in its vegetative stage but
obligately outbreeding. Our pheromone experiments are the first studies in which
gametogenesis has been induced in diatoms by cell-free exudates, opening new
possibilities for molecular 'dissection' of sexualization.
PMID- 22046413
TI - Human RNA polymerase II-association factor 1 (hPaf1/PD2) regulates histone
methylation and chromatin remodeling in pancreatic cancer.
AB - Change in gene expression associated with pancreatic cancer could be attributed
to the variation in histone posttranslational modifications leading to subsequent
remodeling of the chromatin template during transcription. However, the
interconnected network of molecules involved in regulating such processes remains
elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the
regulation of transcriptional elongation has oncogenic potential. Our study
explores the possibility that regulation of histone methylation by hPaf1 can
contribute towards alteration in gene expression by nucleosomal rearrangement.
Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri
methylation at histone H3 lysine 4 residues in pancreatic cancer cells.
Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a
histone methyltransferase that methylates H3K4 residues. Also, a reduction in
hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in
the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent
chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl
marks. hPaf1/PD2 was also found to interact and colocalize with CHD1 in both
cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced
level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be
rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion showed
an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our results
suggest that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4
residues, as well as interacts and regulates nuclear shuttling of chromatin
remodeling protein CHD1, facilitating its function in pancreatic cancer cells.
PMID- 22046414
TI - Analysis of the expression, secretion and translocation of the Salmonella
enterica type III secretion system effector SteA.
AB - Many Gram-negative pathogens possess virulence-related type III secretion
systems. Salmonella enterica uses two of these systems, encoded on the
pathogenicity islands SPI-1 and SPI-2, respectively, to translocate more than 30
effector proteins into eukaryotic host cells. SteA is one of the few effectors
that can be translocated by both systems. We investigated the conditions
affecting the synthesis of this effector, its secretion to culture media and its
translocation into host cells. Whereas steA was expressed under a wide range of
conditions, some factors, including low and high osmolarity, and presence of
butyrate, decreased expression. SteA was efficiently secreted to the culture
media under both SPI-1 and SPI-2 inducing conditions. The kinetics of
translocation into murine macrophages and human epithelial cells was studied
using fusions with the 3xFLAG tag, and fusions with CyaA from Bordetella
pertussis. Translocation into macrophages under non-invasive conditions was
mainly dependent on the SPI-2-encoded type III secretion system but some
participation of the SPI-1 system was also detected 6 hours post-infection.
Interestingly, both type III secretion systems had a relevant role in the
translocation of SteA into epithelial cells. Finally, a deletion approach allowed
the identification of the N-terminal signal necessary for translocation of this
effector. The amino acid residues 1-10 were sufficient to direct translocation
into host cells through both type III secretion systems. Our results provide new
examples of functional overlapping between the two type III secretion systems of
Salmonella.
PMID- 22046415
TI - Antibodies recognizing Mycobacterium avium paratuberculosis epitopes cross-react
with the beta-cell antigen ZnT8 in Sardinian type 1 diabetic patients.
AB - The environmental factors at play in the pathogenesis of type 1 diabetes (T1D)
remain enigmatic. Mycobacterium avium subspecies paratuberculosis (MAP) is
transmitted from dairy herds to humans through food contamination. MAP causes an
asymptomatic infection that is highly prevalent in Sardinian T1D patients
compared with type 2 diabetes (T2D) and healthy controls. Moreover, MAP elicits
humoral responses against several mycobacterial proteins. We asked whether
antibodies (Abs) against one of these proteins, namely MAP3865c, which displays a
sequence homology with the beta-cell protein zinc transporter 8 (ZnT8) could be
cross-reactive with ZnT8 epitopes. To this end, Ab responses against MAP3865c
were analyzed in Sardinian T1D, T2D and healthy subjects using an enzymatic
immunoassay. Abs against MAP3865c recognized two immunodominant transmembrane
epitopes in 52-65% of T1D patients, but only in 5-7% of T2D and 3-5% of healthy
controls. There was a linear correlation between titers of anti-MAP3865c and anti
ZnT8 Abs targeting these two homologous epitopes, and pre-incubation of sera with
ZnT8 epitope peptides blocked binding to the corresponding MAP3865c peptides.
These results demonstrate that Abs recognizing MAP3865c epitopes cross-react with
ZnT8, possibly underlying a molecular mimicry mechanism, which may precipitate
T1D in MAP-infected individuals.
PMID- 22046416
TI - Epilepsy caused by an abnormal alternative splicing with dosage effect of the
SV2A gene in a chicken model.
AB - Photosensitive reflex epilepsy is caused by the combination of an individual's
enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or
video games. This is the most common reflex epilepsy in humans; it is
characterized by the photoparoxysmal response, which is an abnormal
electroencephalographic reaction, and seizures triggered by intermittent light
stimulation. Here, by using genetic mapping, sequencing and functional analyses,
we report that a mutation in the acceptor site of the second intron of SV2A (the
gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex
epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous
model where the neurological disorder is inherited as an autosomal recessive
mutation. This mutation causes an aberrant splicing event and significantly
reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second
generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice
develop seizures soon after birth and usually die within three weeks. The Fepi
chicken survives to adulthood and responds to levetiracetam, suggesting that the
low-level expression of SV2A in these animals is sufficient to allow survival,
but does not protect against seizures. Thus, the Fepi chicken model shows that
the role of the SV2A pathway in the brain is conserved between birds and mammals,
in spite of a large phylogenetic distance. The Fepi model appears particularly
useful for further studies of physiopathology of reflex epilepsy, in comparison
with induced models of epilepsy in rodents. Consequently, SV2A is a very
attractive candidate gene for analysis in the context of both mono- and polygenic
generalized epilepsies in humans.
PMID- 22046417
TI - Transmission dynamics of low pathogenicity avian influenza infections in Turkey
flocks.
AB - Low pathogenicity avian influenza (LPAI) viruses of H5 and H7 subtypes have the
potential to mutate into highly pathogenic strains (HPAI), which can threaten
human health and cause huge economic losses. The current knowledge on the
mechanisms of mutation from LPAI to HPAI is insufficient for predicting which H5
or H7 strains will mutate into an HPAI strain, and since the molecular changes
necessary for the change in virulence seemingly occur at random, the probability
of mutation depends on the number of virus replicates, which is associated with
the number of birds that acquire infection. We estimated the transmission
dynamics of LPAI viruses in turkeys using serosurveillance data from past
epidemics in Italy. We fitted the proportions of birds infected in 36 flocks into
a hierarchical model to estimate the basic reproduction number (R(0)) and
possible variations in R(0) among flocks caused by differences among farms. We
also estimated the distributions of the latent and infectious periods, using
experimental infection data with outbreak strains. These were then combined with
the R(0) to simulate LPAI outbreaks and characterise the resulting dynamics. The
estimated mean within-flock R(0) in the population of infected flocks was 5.5,
indicating that an infectious bird would infect an average of more than five
susceptible birds. The results also indicate that the presence of seropositive
birds does not necessarily mean that the virus has already been cleared and the
flock is no longer infective, so that seropositive flocks may still constitute a
risk of infection for other flocks. In light of these results, the enforcement of
appropriate restrictions, the culling of seropositive flocks, or pre-emptive
slaughtering may be useful. The model and parameter estimates presented in this
paper provide the first complete picture of LPAI dynamics in turkey flocks and
could be used for designing a suitable surveillance program.
PMID- 22046418
TI - Atomic-level characterization of the activation mechanism of SERCA by calcium.
AB - We have performed molecular dynamics (MD) simulations to elucidate, in atomic
detail, the mechanism by which the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA)
is activated by Ca(2+). Crystal structures suggest that activation of SERCA
occurs when the cytoplasmic head-piece, in an open (E1) conformation stabilized
by Ca(2+), undergoes a large-scale open-to-closed (E1 to E2) transition that is
induced by ATP binding. However, spectroscopic measurements in solution suggest
that these structural states (E1 and E2) are not tightly coupled to biochemical
states (defined by bound ligands); the closed E2 state predominates even in the
absence of ATP, in both the presence and absence of Ca(2+). How is this loose
coupling consistent with the high efficiency of energy transduction in the Ca(2+)
ATPase? To provide insight into this question, we performed long (500 ns) all
atom MD simulations starting from the open crystal structure, including a lipid
bilayer and water. In both the presence and absence of Ca(2+), we observed a
large-scale open-to-closed conformational transition within 400 ns, supporting
the weak coupling between structural and biochemical states. However, upon closer
inspection, it is clear that Ca(2+) is necessary and sufficient for SERCA to
reach the precise geometrical arrangement necessary for activation of ATP
hydrolysis. Contrary to suggestions from crystal structures, but in agreement
with solution spectroscopy, the presence of ATP is not required for this
activating transition. Principal component analysis showed that Ca(2+) reshapes
the free energy landscape of SERCA to create a path between the open conformation
and the activated closed conformation. Thus the malleability of the free energy
landscape is essential for SERCA efficiency, ensuring that ATP hydrolysis is
tightly coupled to Ca(2+) transport. These results demonstrate the importance of
real-time dynamics in the formation of catalytically competent conformations of
SERCA, with broad implications for understanding enzymatic catalysis in atomic
detail.
PMID- 22046419
TI - Is fetal growth restriction associated with a more severe maternal phenotype in
the setting of early onset pre-eclampsia? A retrospective study.
AB - BACKGROUND: Both pre-eclampsia and fetal growth restriction are thought to result
from abnormal placental implantation in early pregnancy. Consistent with this
shared pathophysiology, it is not uncommon to see growth restriction further
confound the course of pre-eclampsia and vice versa. It has been previously
suggested that superimposed growth restriction is associated with a more severe
pre-eclamptic phenotype, however this has not been a consistent finding.
Therefore, we set out to determine whether the presence of fetal growth
restriction among women with severe early-onset pre-eclampsia was associated with
more severe maternal disease compared to those without a growth-restricted fetus.
METHODS AND FINDINGS: We undertook a retrospective cohort study of women
presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34
weeks' gestation) between 2005-2009. We collected clinical data, including
severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe
pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction.
However, no significant difference was seen in relation to the severity of pre
eclampsia between those with or without a growth-restricted baby. The presence of
concomitant growth restriction was however associated with a significantly
increased risk of stillbirth (p = 0.003) and total perinatal mortality (p =
0.02). CONCLUSIONS: The presence of fetal growth restriction among women with
severe early-onset pre-eclampsia is not associated with increased severity of
maternal disease. However the incidence of stillbirth and perinatal death is
significantly increased in this sub-population.
PMID- 22046420
TI - Functional correlations of pathogenesis-driven gene expression signatures in
tuberculosis.
AB - Tuberculosis remains a major health threat and its control depends on improved
measures of prevention, diagnosis and treatment. Biosignatures can play a
significant role in the development of novel intervention measures against TB and
blood transcriptional profiling is increasingly exploited for their rational
design. Such profiles also reveal fundamental biological mechanisms associated
with the pathology of the disease. We have compared whole blood gene expression
in TB patients, as well as in healthy infected and uninfected individuals in a
cohort in The Gambia, West Africa and validated previously identified signatures
showing high similarities of expression profiles among different cohorts. In this
study, we applied a unique combination of classical gene expression analysis with
pathway and functional association analysis integrated with intra-individual
expression correlations. These analyses were employed for identification of new
disease-associated gene signatures, identifying a network of Fc gamma receptor 1
signaling with correlating transcriptional activity as hallmark of gene
expression in TB. Remarkable similarities to characteristic signatures in the
autoimmune disease systemic lupus erythematosus (SLE) were observed. Functional
gene clusters of immunoregulatory interactions involving the JAK-STAT pathway;
sensing of microbial patterns by Toll-like receptors and IFN-signaling provide
detailed insights into the dysregulation of critical immune processes in TB,
involving active expression of both pro-inflammatory and immunoregulatory
systems. We conclude that transcriptomics (i) provides a robust system for
identification and validation of biosignatures for TB and (ii) application of
integrated analysis tools yields novel insights into functional networks
underlying TB pathogenesis.
PMID- 22046421
TI - A common genetic variant (97906C>A) of DAB2IP/AIP1 is associated with an
increased risk and early onset of lung cancer in Chinese males.
AB - DOC-2/DAB2 interactive protein (DAB2IP) is a novel identified tumor suppressor
gene that inhibits cell growth and facilitates cell apoptosis. One genetic
variant in DAB2IP gene was reported to be associated with an increased risk of
aggressive prostate cancer recently. Since DAB2IP involves in the development of
lung cancer and low expression of DAB2IP are observed in lung cancer, we
hypothesized that the variations in DAB2IP gene can increase the genetic
susceptibility to lung cancer. In a case-control study of 1056 lung cancer cases
and 1056 sex and age frequency-matched cancer-free controls, we investigated the
association between two common polymorphisms in DAB2IP gene (-1420T>G, rs7042542;
97906C>A, rs1571801) and the risk of lung cancer. We found that compared with the
97906CC genotypes, carriers of variant genotypes (97906AC+AA) had a significant
increased risk of lung cancer (adjusted odds ratio [OR] = 1.33, 95%CI = 1.04
1.70, P = 0.023) and the number of variant (risk) allele worked in a dose
response manner (P(trend) = 0.0158). Further stratification analysis showed that
the risk association was more pronounced in subjects aged less than 60 years old,
males, non-smokers, non-drinkers, overweight groups and in those with family
cancer history in first or second-degree relatives, and the 97906A interacted
with overweight on lung cancer risk. We further found the number of risk alleles
(97906A allele) were negatively correlated with early diagnosis age of lung
cancer in male patients (P = 0.003). However, no significant association was
observed on the -1420T>G polymorphism. Our data suggested that the 97906A variant
genotypes are associated with the increased risk and early onset of lung cancer,
particularly in males.
PMID- 22046422
TI - How frontoparietal brain regions mediate imitative and complementary actions: an
FMRI study.
AB - The 'mirror neuron system' (MNS), located within inferior parietal lobe (IPL) and
inferior frontal gyrus (IFG), creates an internal motor representation of the
actions we see and has been implicated in imitation. Recently, the MNS has been
implicated in non-identical responses: when the actions we must execute do not
match those that we observe. However, in such conflicting situations non action
specific cognitive control networks also located in frontoparietal regions may be
involved. In the present functional magnetic resonance imaging (fMRI) study
participants made both similar and dissimilar actions within two action contexts:
imitative and complementary. We aimed to determine whether activity within
IPL/IFG depends on (i) responding under an imitative versus complementary context
(ii) responding with similar versus dissimilar responses, and (iii) observing
hand actions versus symbolic arrow cue stimuli. Activity within rIPL/rIFG regions
was largest during observation of hand actions compared with arrow cues.
Specifically, rIPL/rIFG were recruited only during the imitative context, when
participants responded with similar actions. When responding to symbolic arrow
cues, rIPL/rIFG activity increased during dissimilar responses, reflecting
increased demands placed on general cognitive control mechanisms. These results
suggest a specific role of rIPL/rIFG during imitation of hand actions, and also a
general role of frontoparietal areas in mediating dissimilar responses to both
hand actions and symbolic stimuli. We discuss our findings in relation to recent
work that has examined the role of frontoparietal brain structures in joint
actions and inter-actor cooperation. We conclude that the specific brain regions
identified here to show increased activation during action observation conditions
are likely to form part of a mechanism specifically involved in matching observed
actions directly with internal motor plans. Conversely, observation of arrow cues
recruited part of a wider cognitive control network involved in the rapid
remapping of stimulus-response associations.
PMID- 22046423
TI - Palmitate-activated macrophages confer insulin resistance to muscle cells by a
mechanism involving protein kinase C theta and epsilon.
AB - BACKGROUND: Macrophage-derived factors contribute to whole-body insulin
resistance, partly by impinging on metabolically active tissues. As proof of
principle for this interaction, conditioned medium from macrophages treated with
palmitate (CM-PA) reduces insulin action and glucose uptake in muscle cells.
However, the mechanism whereby CM-PA confers this negative response onto muscle
cells remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: L6-GLUT4myc myoblasts were
exposed for 24 h to palmitate-free conditioned medium from RAW 264.7 macrophages
pre-treated with 0.5 mM palmitate for 6 h. This palmitate-free CM-PA, containing
selective cytokines and chemokines, inhibited myoblast insulin-stimulated insulin
receptor substrate 1 (IRS1) tyrosine phosphorylation, AS160 phosphorylation,
GLUT4 translocation and glucose uptake. These effects were accompanied by a rise
in c-Jun N-terminal kinase (JNK) activation, degradation of Inhibitor of
kappaBalpha (IkappaBalpha), and elevated expression of proinflammatory cytokines
in myoblasts. Notably, CM-PA caused IRS1 phosphorylation on Ser1101, and
phosphorylation of novel PKCtheta and epsilon. Co-incubation of myoblasts with CM
PA and the novel and conventional PKC inhibitor Go6983 (but not with the
conventional PKC inhibitor Go6976) prevented PKCtheta and epsilon activation, JNK
phosphorylation, restored IkappaBalpha mass and reduced proinflammatory cytokine
production. Go6983 also restored insulin signalling and glucose uptake in
myoblasts. Moreover, co-silencing both novel PKC theta and epsilon isoforms in
myoblasts by RNA interference, but not their individual silencing, prevented the
inflammatory response and restored insulin sensitivity to CM-PA-treated
myoblasts. CONCLUSIONS/CLINICAL SIGNIFICANCE: The results suggest that the block
in muscle insulin action caused by CM-PA is mediated by novel PKCtheta and
PKCepsilon. This study re-establishes the participation of macrophages as a relay
in the action of fatty acids on muscle cells, and further identifies PKCtheta and
PKCepsilon as key elements in the inflammatory and insulin resistance responses
of muscle cells to macrophage products. Furthermore, it portrays these PKC
isoforms as potential targets for the treatment of fatty acid-induced,
inflammation-linked insulin resistance.
PMID- 22046424
TI - Quantitative bias in Illumina TruSeq and a novel post amplification barcoding
strategy for multiplexed DNA and small RNA deep sequencing.
AB - Here we demonstrate a method for unbiased multiplexed deep sequencing of RNA and
DNA libraries using a novel, efficient and adaptable barcoding strategy called
Post Amplification Ligation-Mediated (PALM). PALM barcoding is performed as the
very last step of library preparation, eliminating a potential barcode-induced
bias and allowing the flexibility to synthesize as many barcodes as needed. We
sequenced PALM barcoded micro RNA (miRNA) and DNA reference samples and evaluated
the quantitative barcode-induced bias in comparison to the same reference samples
prepared using the Illumina TruSeq barcoding strategy. The Illumina TruSeq small
RNA strategy introduces the barcode during the PCR step using differentially
barcoded primers, while the TruSeq DNA strategy introduces the barcode before the
PCR step by ligation of differentially barcoded adaptors. Results show virtually
no bias between the differentially barcoded miRNA and DNA samples, both for the
PALM and the TruSeq sample preparation methods. We also multiplexed miRNA
reference samples using a pre-PCR barcode ligation. This barcoding strategy
results in significant bias.
PMID- 22046425
TI - Postoperative adverse outcomes in intellectually disabled surgical patients: a
nationwide population-based study.
AB - BACKGROUND: Intellectually disabled patients have various comorbidities, but
their risks of adverse surgical outcomes have not been examined. This study
assesses pre-existing comorbidities, adjusted risks of postoperative major
morbidities and mortality in intellectually disabled surgical patients. METHODS:
A nationwide population-based study was conducted in patients who underwent
inpatient major surgery in Taiwan between 2004 and 2007. Four controls for each
patient were randomly selected from the National Health Insurance Research
Database. Preoperative major comorbidities, postoperative major complications and
30-day in-hospital mortality were compared between patients with and without
intellectual disability. Use of medical services also was analyzed. Adjusted odds
ratios using multivariate logistic regression analyses with 95% confidence
intervals were applied to verify intellectual disability's impact. RESULTS:
Controls were compared with 3983 surgical patients with intellectual disability.
Risks for postoperative major complications were increased in patients with
intellectual disability, including acute renal failure (odds ratio 3.81, 95%
confidence interval 2.28 to 6.37), pneumonia (odds ratio 2.01, 1.61 to 2.49),
postoperative bleeding (odds ratio 1.35, 1.09 to 1.68) and septicemia (odds ratio
2.43, 1.85 to 3.21) without significant differences in overall mortality.
Disability severity was positively correlated with postoperative septicemia risk.
Medical service use was also significantly higher in surgical patients with
intellectual disability. CONCLUSION: Intellectual disability significantly
increases the risk of overall major complications after major surgery. Our
findings show a need for integrated and revised protocols for postoperative
management to improve care for intellectually disabled surgical patients.
PMID- 22046427
TI - Altering host resistance to infections through microbial transplantation.
AB - Host resistance to bacterial infections is thought to be dictated by host genetic
factors. Infections by the natural murine enteric pathogen Citrobacter rodentium
(used as a model of human enteropathogenic and enterohaemorrhagic E. coli
infections) vary between mice strains, from mild self-resolving colonization in
NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component
had been shown to be responsible for the differences observed with C. rodentium
infections. Because the intestinal microbiota is important in regulating
resistance to infection, and microbial composition is dependent on host genotype,
it was tested whether variations in microbial composition between mouse strains
contributed to differences in "host" susceptibility by transferring the
microbiota of resistant mice to lethally susceptible mice prior to infection.
Successful transfer of the microbiota from resistant to susceptible mice resulted
in delayed pathogen colonization and mortality. Delayed mortality was associated
with increased IL-22 mediated innate defense including antimicrobial peptides
Reg3gamma and Reg3beta, and immunono-neutralization of IL-22 abrogated the
beneficial effect of microbiota transfer. Conversely, depletion of the native
microbiota in resistant mice by antibiotics and transfer of the susceptible mouse
microbiota resulted in reduced innate defenses and greater pathology upon
infection. This work demonstrates the importance of the microbiota and how it
regulates mucosal immunity, providing an important factor in susceptibility to
enteric infection. Transfer of resistance through microbial transplantation
(bacteriotherapy) provides additional mechanisms to alter "host" resistance, and
a novel means to alter enteric infection and to study host-pathogen interactions.
PMID- 22046428
TI - Genetic ablation of PLA2G6 in mice leads to cerebellar atrophy characterized by
Purkinje cell loss and glial cell activation.
AB - Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive
neurodegenerative disease characterized by axonal dystrophy, abnormal iron
deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6,
which encodes group VI Ca(2+)-independent phospholipase A(2) (iPLA(2) or
iPLA(2)beta). Here we show that genetic ablation of PLA2G6 in mice (iPLA(2)beta(
/-)) leads to the development of cerebellar atrophy by the age of 13 months.
Atrophied cerebella exhibited significant loss of Purkinje cells, as well as
reactive astrogliosis, the activation of microglial cells, and the pronounced up
regulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF
alpha) and interleukin-1beta (IL-1beta). Moreover, glial cell activation and the
elevation in TNF-alpha and IL-1beta expression occurred before apparent
cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes
neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar
atrophy. Our study suggests that iPLA(2)beta(-/-) mice are a valuable model for
cerebellar atrophy in INAD and that early anti-inflammatory therapy may help slow
the progression of cerebellar atrophy in this deadly neurodegenerative disease.
PMID- 22046429
TI - Urocortin-1 within the centrally-projecting Edinger-Westphal nucleus is critical
for ethanol preference.
AB - Converging lines of evidence point to the involvement of neurons of the centrally
projecting Edinger-Westphal nucleus (EWcp) containing the neuropeptide Urocortin
1 (Ucn1) in excessive ethanol (EtOH) intake and EtOH sensitivity. Here, we
expanded these previous findings by using a continuous-access, two-bottle choice
drinking paradigm (3%, 6%, and 10% EtOH vs. tap water) to compare EtOH intake and
EtOH preference in Ucn1 genetic knockout (KO) and wild-type (WT) mice. Based on
previous studies demonstrating that electrolytic lesion of the EWcp attenuated
EtOH intake and preference in high-drinking C57BL/6J mice, we also set out to
determine whether EWcp lesion would differentially alter EtOH consumption in Ucn1
KO and WT mice. Finally, we implemented well-established place conditioning
procedures in KO and WT mice to determine whether Ucn1 and the corticotropin
releasing factor type-2 receptor (CRF-R2) were involved in the rewarding and
aversive effects of EtOH (2 g/kg, i.p.). Results from these studies revealed that
(1) genetic deletion of Ucn1 dampened EtOH preference only in mice with an intact
EWcp, but not in mice that received lesion of the EWcp, (2) lesion of the EWcp
dampened EtOH intake in Ucn1 KO and WT mice, but dampened EtOH preference only in
WT mice expressing Ucn1, and (3) genetic deletion of Ucn1 or CRF-R2 abolished the
conditioned rewarding effects of EtOH, but deletion of Ucn1 had no effect on the
conditioned aversive effects of EtOH. The current findings provide strong support
for the hypothesis that EWcp-Ucn1 neurons play an important role in EtOH intake,
preference, and reward.
PMID- 22046426
TI - Structural basis for broad neutralization of hepatitis C virus quasispecies.
AB - Monoclonal antibodies directed against hepatitis C virus (HCV) E2 protein can
neutralize cell-cultured HCV and pseudoparticles expressing envelopes derived
from multiple HCV subtypes. For example, based on antibody blocking experiments
and alanine scanning mutagenesis, it was proposed that the AR3B monoclonal
antibody recognized a discontinuous conformational epitope comprised of amino
acid residues 396-424, 436-447, and 523-540 of HCV E2 envelope protein.
Intriguingly, one of these segments (436-447) overlapped with hypervariable
region 3 (HVR3), a domain that exhibited significant intrahost and interhost
genetic diversity. To reconcile these observations, amino-acid sequence
variability was examined and homology-based structural modelling of E2 based on
tick-borne encephalitis virus (TBEV) E protein was performed based on 413 HCV
sequences derived from 18 subjects with chronic hepatitis C. Here we report that
despite a high degree of amino-acid sequence variability, the three-dimensional
structure of E2 is remarkably conserved, suggesting broad recognition of
structural determinants rather than specific residues. Regions 396-424 and 523
540 were largely exposed and in close spatial proximity at the surface of E2. In
contrast, region 436-447, which overlaps with HVR3, was >35 A away, and estimates
of buried surface were inconsistent with HVR3 being part of the AR3B binding
interface. High-throughput structural analysis of HCV quasispecies could
facilitate the development of novel vaccines that target conserved structural
features of HCV envelope and elicit neutralizing antibody responses that are less
vulnerable to viral escape.
PMID- 22046430
TI - RNA-Seq reveals an integrated immune response in nucleated erythrocytes.
AB - BACKGROUND: Throughout the primary literature and within textbooks, the
erythrocyte has been tacitly accepted to have maintained a unique physiological
role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated
erythrocytes are present in circulation throughout the life cycle and a
fragmented series of observations in mammals support a potential role in non
respiratory biological processes. We hypothesised that nucleated erythrocytes
could actively participate via ligand-induced transcriptional re-programming in
the immune response. METHODOLOGY/PRINCIPAL FINDINGS: Nucleated erythrocytes from
both fish and birds express and regulate specific pattern recognition receptor
(PRR) mRNAs and, thus, are capable of specific pathogen associated molecular
pattern (PAMP) detection that is central to the innate immune response. In vitro
challenge with diverse PAMPs led to de novo specific mRNA synthesis of both
receptors and response factors including interferon-alpha (IFNalpha) that exhibit
a stimulus-specific polysomal shift supporting active translation. RNA-Seq
analysis of the PAMP (Poly (I:C), polyinosinic:polycytidylic acid)-erythrocyte
response uncovered diverse cohorts of differentially expressed mRNA transcripts
related to multiple physiological systems including the endocrine, reproductive
and immune. Moreover, erythrocyte-derived conditioned mediums induced a type-1
interferon response in macrophages thus supporting an integrative role for the
erythrocytes in the immune response. CONCLUSIONS/SIGNIFICANCE: We demonstrate
that nucleated erythrocytes in non-mammalian vertebrates spanning significant
phylogenetic distance participate in the immune response. RNA-Seq studies
highlight a mRNA repertoire that suggests a previously unrecognized integrative
role for the erythrocytes in other physiological systems.
PMID- 22046431
TI - Evolutionary history of the vertebrate mitogen activated protein kinases family.
AB - BACKGROUND: The mitogen activated protein kinases (MAPK) family pathway is
implicated in diverse cellular processes and pathways essential to most
organisms. Its evolution is conserved throughout the eukaryotic kingdoms.
However, the detailed evolutionary history of the vertebrate MAPK family is
largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: The MAPK family members were
collected from literatures or by searching the genomes of several vertebrates and
invertebrates with the known MAPK sequences as queries. We found that vertebrates
had significantly more MAPK family members than invertebrates, and the vertebrate
MAPK family originated from 3 progenitors, suggesting that a burst of gene
duplication events had occurred after the divergence of vertebrates from
invertebrates. Conservation of evolutionary synteny was observed in the
vertebrate MAPK subfamilies 4, 6, 7, and 11 to 14. Based on synteny and
phylogenetic relationships, MAPK12 appeared to have arisen from a tandem
duplication of MAPK11 and the MAPK13-MAPK14 gene unit was from a segmental
duplication of the MAPK11-MAPK12 gene unit. Adaptive evolution analyses reveal
that purifying selection drove the evolution of MAPK family, implying strong
functional constraints of MAPK genes. Intriguingly, however, intron losses were
specifically observed in the MAPK4 and MAPK7 genes, but not in their flanking
genes, during the evolution from teleosts to amphibians and mammals. The specific
occurrence of intron losses in the MAPK4 and MAPK7 subfamilies might be
associated with adaptive evolution of the vertebrates by enhancing the gene
expression level of both MAPK genes. CONCLUSIONS/SIGNIFICANCE: These results
provide valuable insight into the evolutionary history of the vertebrate MAPK
family.
PMID- 22046432
TI - Dissolution of pre-existing platelet thrombus by synergistic administration of
low concentrations of bifunctional antibodies against beta3 integrin.
AB - Most antithrombotic approaches target prevention rather than the more clinically
relevant issue of resolution of an existing thrombus. In this study, we describe
a novel and effective therapeutic strategy for ex vivo clearance of pre-existing
platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66
ligands that target different parts of the arterial thrombus. We produced an
additional GPIIIa49-66 agent (named APAC), which homes to activated platelets.
Like our previously described SLK (which targets newly deposited fibrin strands
surrounding the platelet thrombus), APAC destroys platelet aggregates ex vivo in
an identical fashion with 85% destruction of platelet aggregates at 2 hours. The
combined application of APAC and SLK demonstrated a ~2 fold greater platelet
thrombus dissolution than either agent alone at a low concentration (0.025 uM).
Platelet-rich clot lysis experiments demonstrated the time required for 50%
platelet-rich fibrin clot lysis (T(50%)) by APAC (95 +/- 6.1 min) or SLK (145 +/-
7.1 min) was much longer than that by combined APAC + SLK (65 +/- 7.6 min) at the
final concentration of 0.025 uM (APAC + SLK vs APAC, p<0.05; APAC + SLK vs SLK,
p<0.01). Thus these low concentrations of a combination of both agents are likely
to be more effective and less toxic when used therapeutically in vivo.
PMID- 22046433
TI - Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes
developmental delay, cardiovascular defects, and early embryonic lethality.
AB - Familial Dysautonomia (FD) is an autosomal recessive disorder that affects
1/3,600 live births in the Ashkenazi Jewish population, and leads to death before
the age of 40. The disease is characterized by abnormal development and
progressive degeneration of the sensory and autonomic nervous system. A single
base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD
cases, and results in the expression of low levels of the full-length mRNA with
simultaneous expression of an aberrantly spliced mRNA in which exon 20 is
missing. To date, there is no animal model for the disease, and the essential
cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To
better understand the normal function of IKAP and in an effort to generate a
mouse model for FD, we have targeted the mouse Ikbkap gene by homologous
recombination. We created two distinct alleles that result in either loss of
Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity
for either mutation leads to developmental delay, cardiovascular and brain
malformations, accompanied with early embryonic lethality. Our analyses indicate
that IKAP is essential for expression of specific genes involved in cardiac
morphogenesis, and that cardiac failure is the likely cause of abnormal vascular
development and embryonic lethality. Our results also indicate that deletion of
exon 20 abolishes gene function. This implies that the truncated IKAP protein
expressed in FD patients does not retain any significant biological function.
PMID- 22046434
TI - Overexpression of a minimal domain of calpastatin suppresses IL-6 production and
Th17 development via reduced NF-kappaB and increased STAT5 signals.
AB - Calpain, a calcium-dependent cysteine protease, is reportedly involved in the
pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA). In
addition, autoantibodies against calpastatin, a natural and specific inhibitor of
calpain, are widely observed in RA. We previously reported that E-64-d, a
membrane-permeable cysteine protease inhibitor, is effective in treating
experimental arthritis. However, the exact role of the calpastatin-calpain
balance in primary inflammatory cells remains unclear. Here we investigated the
effect of calpain-specific inhibition by overexpressing a minimal functional
domain of calpastatin in primary helper T (Th) cells, primary fibroblasts from RA
patients, and fibroblast cell lines. We found that the calpastatin-calpain
balance varied during Th1, Th2, and Th17 development, and that overexpression of
a minimal domain of calpastatin (by retroviral gene transduction) or the
inhibition of calpain by E-64-d suppressed the production of IL-6 and IL-17 by Th
cells and the production of IL-6 by fibroblasts. These suppressions were
associated with reductions in RORgammat expression and STAT3 phosphorylation.
Furthermore, inhibiting calpain by silencing its small regulatory subunit (CPNS)
suppressed Th17 development. We also confirmed that overexpressing a minimal
domain of calpastatin suppressed IL-6 by reducing NF-kappaB signaling via the
stabilization of IkappaBalpha, without affecting the upstream signal. Moreover,
our findings indicated that calpastatin overexpression suppressed IL-17
production by Th cells by up-regulating the STAT5 signal. Finally, overexpression
of a minimal domain of calpastatin suppressed IL-6 production efficiently in
primary fibroblasts derived from the RA synovium. These findings suggest that
inhibiting calpain by overexpressing a minimal domain of calpastatin could
coordinately suppress proinflammatory activities, not only those of Th cells but
also of synovial fibroblasts. Thus, this strategy may prove viable as a candidate
treatment for inflammatory diseases such as RA.
PMID- 22046435
TI - Deep sequencing the transcriptome reveals seasonal adaptive mechanisms in a
hibernating mammal.
AB - Mammalian hibernation is a complex phenotype involving metabolic rate reduction,
bradycardia, profound hypothermia, and a reliance on stored fat that allows the
animal to survive for months without food in a state of suspended animation. To
determine the genes responsible for this phenotype in the thirteen-lined ground
squirrel (Ictidomys tridecemlineatus) we used the Roche 454 platform to sequence
mRNA isolated at six points throughout the year from three key tissues: heart,
skeletal muscle, and white adipose tissue (WAT). Deep sequencing generated
approximately 3.7 million cDNA reads from 18 samples (6 time points *3 tissues)
with a mean read length of 335 bases. Of these, 3,125,337 reads were assembled
into 140,703 contigs. Approximately 90% of all sequences were matched to proteins
in the human UniProt database. The total number of distinct human proteins
matched by ground squirrel transcripts was 13,637 for heart, 12,496 for skeletal
muscle, and 14,351 for WAT. Extensive mitochondrial RNA sequences enabled a novel
approach of using the transcriptome to construct the complete mitochondrial
genome for I. tridecemlineatus. Seasonal and activity-specific changes in mRNA
levels that met our stringent false discovery rate cutoff (1.0 * 10(-11)) were
used to identify patterns of gene expression involving various aspects of the
hibernation phenotype. Among these patterns are differentially expressed genes
encoding heart proteins AT1A1, NAC1 and RYR2 controlling ion transport required
for contraction and relaxation at low body temperatures. Abundant RNAs in
skeletal muscle coding ubiquitin pathway proteins ASB2, UBC and DDB1 peak in
October, suggesting an increase in muscle proteolysis. Finally, genes in WAT that
encode proteins involved in lipogenesis (ACOD, FABP4) are highly expressed in
August, but gradually decline in expression during the seasonal transition to
lipolysis.
PMID- 22046436
TI - Categorization of extremely brief auditory stimuli: domain-specific or domain
general processes?
AB - The present study investigated the minimum amount of auditory stimulation that
allows differentiation of spoken voices, instrumental music, and environmental
sounds. Three new findings were reported. 1) All stimuli were categorized above
chance level with 50 ms-segments. 2) When a peak-level normalization was applied,
music and voices started to be accurately categorized with 20 ms-segments. When
the root-mean-square (RMS) energy of the stimuli was equalized, voice stimuli
were better recognized than music and environmental sounds. 3) Further
psychoacoustical analyses suggest that the categorization of extremely brief
auditory stimuli depends on the variability of their spectral envelope in the
used set. These last two findings challenge the interpretation of the voice
superiority effect reported in previously published studies and propose a more
parsimonious interpretation in terms of an emerging property of auditory
categorization processes.
PMID- 22046437
TI - CARM1 mediates modulation of Sox2.
AB - Sox2 is a key component of the transcription factor network that maintains the
pluripotent state of embryonic stem cells (ESCs). Sox2 is regulated by multiple
post-translational modifications, including ubiquitination, sumoylation,
acetylation and phosphorylation. Here we report that Sox2 is in association with
and methylated by coactivator-associated arginine methyltransferase 1 (CARM1), a
protein arginine methyltransferase that plays a pivotal role in ESCs. We found
that CARM1 facilitates Sox2-mediated transactivation and directly methylates Sox2
at arginine 113. This methylation event enhances Sox2 self-association.
Furthermore, the physiological retention of Sox2 on chromatin restricts the Sox2
methylation level. Our study reveals the direct regulation of Sox2 by CARM1 that
sheds lights on how arginine methylation signals are integrated into the
pluripotent transcription factor network.
PMID- 22046438
TI - Bacterial-epithelial contact is a key determinant of host innate immune responses
to enteropathogenic and enteroaggregative Escherichia coli.
AB - BACKGROUND: Enteropathogenic (EPEC) and Enteroaggregative (EAEC) E. coli have
similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless
when they infect the gastrointestinal tract, it is thought that their flagellin
causes IL-8 release leading to neutrophil recruitment and gastroenteritis.
However, this may not be the whole story as the effect of bacterial adherence to
IEC innate response(s) remains unclear. Therefore, we have characterized which
bacterial motifs contribute to the innate epithelial response to EPEC and EAEC,
using a range of EPEC and EAEC isogenic mutant strains. METHODOLOGY: Caco-2 and
HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain
O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non
adherent, type three secretion system (TTSS) negative, signalling negative] or
O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured.
Bacterial surface structures were assessed by negative staining Transmission
Electron Microscopy. The Fluorescent-actin staining test was carried out to
determine bacterial adherence. RESULTS: Previous studies have reported a balance
between the host pro-inflammatory response and microbial suppression of this
response. In our system an overall balance towards the host pro-inflammatory
response is seen with the E69 WT and to a greater extent O42 WT, which is in fit
with clinical symptoms. On removal of the external EPEC structures flagella, LPS,
BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is
reduced. However, removal of E69 lymphostatin increases the host inflammatory
response suggesting involvement in the bacterial mediated anti-inflammatory
response. CONCLUSION: Epithelial responses were due to combinations of bacterial
agonists, with host-bacterial contact a key determinant of these innate
responses. Host epithelial recognition was offset by the microbe's ability to
down-regulate the inflammatory response. Understanding the complexity of this
host-microbial balance will contribute to improved vaccine design for infectious
gastroenteritis.
PMID- 22046439
TI - Serum A-FABP is increased and closely associated with elevated NT-proBNP levels
in type 2 diabetic patients treated with rosiglitazone.
AB - BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) has been shown to play
important roles in the development of metabolic syndrome, diabetes, and
cardiovascular diseases. In this study we investigated the possible role of A
FABP in the development of cardiac dysfunction related to rosiglitazone
treatment. METHODOLOGY/PRINCIPAL FINDINGS: A total of 84 patients with newly
diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks.
Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP)
levels were determined at baseline and repeated at 24 and 48 weeks. After the 48
week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP
increased progressively and significantly (P<0.01). Serum levels of A-FABP were
demonstrated to be positively correlated with gender and waist circumference both
at baseline and the end of the study, and with age, body mass index (BMI), total
cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C),
and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were
significantly and positively correlated with changes in NT-proBNP (r = 0.239, P =
0.039). Furthermore, multiple stepwise regression analysis showed that the
changes in A-FABP were independently and positively associated with changes in NT
proBNP after adjusting for confounding factors (beta = 0.320, P = 0.007).
CONCLUSIONS/SIGNIFICANCE: Rosiglitazone-mediated increase of A-FABP is closely
associated with the elevation of NT-proBNP, a well-established marker of cardiac
dysfunction. The findings of our study imply that A-FABP may mediate the cross
talk between heart and adipose tissue.
PMID- 22046440
TI - Acetylation of the pro-apoptotic factor, p53 in the hippocampus following
cerebral ischemia and modulation by estrogen.
AB - BACKGROUND: Recent studies demonstrate that acetylation of the transcription
factor, p53 on lysine(373) leads to its enhanced stabilization/activity and
increased susceptibility of cells to stress. However, it is not known whether
acetylation of p53 is altered in the hippocampus following global cerebral
ischemia (GCI) or is regulated by the hormone, 17beta-estradiol (17beta-E(2)),
and thus, this study examined these issues. METHODOLOGY/PRINCIPAL FINDINGS: The
study revealed that Acetyl p53-Lysine(373) levels were markedly increased in the
hippocampal CA1 region after GCI at 3 h, 6 h and 24 h after reperfusion, an
effect strongly attenuated by 17beta-E(2). 17beta-E(2) also enhanced interaction
of p53 with the ubiquitin ligase, Mdm2, increased ubiquitination of p53, and
induced its down-regulation, as well as attenuated elevation of the p53
transcriptional target, Puma. We also observed enhanced acetylation of p53 at a
different lysine (Lys(382)) at 3 h after reperfusion, and 17beta-E(2) also
markedly attenuated this effect. Furthermore, administration of an inhibitor of
CBP/p300 acetyltransferase, which acetylates p53, was strongly neuroprotective of
the CA1 region following GCI. In long-term estrogen deprived (LTED) animals, the
ability of 17beta-E(2) to attenuate p53 acetylation was lost, and intriguingly,
Acetyl p53-Lysine(373) levels were markedly elevated in sham (non-ischemic) LTED
animals. Finally, intracerebroventricular injections of Gp91ds-Tat, a specific
NADPH oxidase (NOX2) inhibitor, but not the scrambled tat peptide control (Sc
Tat), attenuated acetylation of p53 and reduced levels of Puma following GCI.
CONCLUSIONS/SIGNIFICANCE: The studies demonstrate that p53 undergoes enhanced
acetylation in the hippocampal CA1 region following global cerebral ischemia, and
that the neuroprotective agent, 17beta-E(2), markedly attenuates the ischemia
induced p53 acetylation. Furthermore, following LTED, the suppressive effect of
17beta-E(2) on p53 acetylation is lost, and p53 acetylation increases in the
hippocampus, which may explain previous reports of increased sensitivity of the
hippocampus to ischemic stress following LTED.
PMID- 22046441
TI - IFI16 protein mediates the anti-inflammatory actions of the type-I interferons
through suppression of activation of caspase-1 by inflammasomes.
AB - BACKGROUND: Type-I interferons (IFNs) are used to treat certain inflammatory
diseases. Moreover, activation of type-I IFN-signaling in immune cells inhibits
the production of proinflammatory cytokines and activation of inflammasomes.
However, the molecular mechanisms remain largely unknown. Upon sensing cytosolic
double-stranded DNA, the AIM2 protein forms the AIM2-ASC inflammasome, resulting
in activation of caspase-1. Given that the IFI16 and AIM2 proteins are IFN
inducible and can heterodimerize with each other, we investigated the regulation
of IFI16, AIM2, and inflammasome proteins by type-I and type-II IFNs and explored
whether the IFI16 protein could negatively regulate the activation of the AIM2
(or other) inflammasome. METHODOLOGY/ PRINCIPAL FINDINGS: We found that basal
levels of the IFI16 and AIM2 proteins were relatively low in peripheral blood
monocytes (CD14(+)) and in the THP-1 monocytic cell line. However, treatment of
THP-1 cells with type-I (IFN-alpha or beta) or type-II (IFN-gamma) IFN induced
the expression levels of IFI16, AIM2, ASC and CASP1 proteins. The induced levels
of IFI16 and AIM2 proteins were detected primarily in the cytoplasm. Accordingly,
relatively more IFI16 protein bound with the AIM2 protein in the cytoplasmic
fraction. Notably, increased expression of IFI16 protein in transfected HEK-293
cells inhibited activation of caspase-1 by the AIM2-ASC inflammasome. Moreover,
the constitutive knockdown of the IFI16 expression in THP-1 cells increased the
basal and induced [induced by poly(dA:dT) or alum] activation of the caspase-1 by
the AIM2 and NLRP3 inflammasomes. CONCLUSIONS/SIGNIFICANCE: Our observations
revealed that the type-I and type-II IFNs induce the expression of IFI16, AIM2,
and inflammasome proteins to various extents in THP-1 cells and the expression of
IFI16 protein in THP-1 cells suppresses the activation of caspase-1 by the AIM2
and NLRP3 inflammasomes. Thus, our observations identify the IFI16 protein as a
mediator of the anti-inflammatory actions of the type-I IFNs.
PMID- 22046442
TI - Sensitization of glioma cells to tamoxifen-induced apoptosis by Pl3-kinase
inhibitor through the GSK-3beta/beta-catenin signaling pathway.
AB - Malignant gliomas represent one of the most aggressive types of cancers and their
recurrence is closely linked to acquired therapeutic resistance. A combination of
chemotherapy is considered a promising therapeutic model in overcoming
therapeutic resistance and enhancing treatment efficacy. Herein, we show by
colony formation, Hochest 33342 and TUNEL staining, as well as by flow cytometric
analysis, that LY294002, a specific phosphatidylinositide-3-kinase (PI3K)
inhibitor, enhanced significantly the sensitization of a traditional cytotoxic
chemotherapeutic agent, tamoxifen-induced apoptosis in C6 glioma cells.
Activation of PI3K signaling pathway by IGF-1 protected U251 cells from apoptosis
induced by combination treatment of LY294002 and tamoxifen. Interference of PI3K
signaling pathway by PI3K subunit P85 siRNA enhanced the sensitization of U251
glioma cells to tamoxifen -induced apoptosis. By Western blotting, we found that
combination treatment showed lower levels of phosphorylated Akt(Ser473) and GSK
3beta(Ser9) than a single treatment of LY294002. Further, we showed a significant
decrease of nuclear beta-catenin by combination treatment. In response to the
inhibition of beta-catenin signaling, mRNA and protein levels of Survivin and the
other three antiapoptotic genes Bcl-2, Bcl-xL, and Mcl-1 were significantly
decreased by combination treatment. Our results indicated that the synergistic
cytotoxic effect of LY294002 and tamoxifen is achieved by the inhibition of GSK
3beta/beta-catenin signaling pathway.
PMID- 22046443
TI - Within- and across-species responses of plant traits and litter decomposition to
elevation across contrasting vegetation types in subarctic tundra.
AB - Elevational gradients are increasingly recognized as a valuable tool for
understanding how community and ecosystem properties respond to climatic factors,
but little is known about how plant traits and their effects on ecosystem
processes respond to elevation. We studied the response of plant leaf and litter
traits, and litter decomposability across a gradient of elevation, and thus
temperature, in subarctic tundra in northern Sweden for each of two contrasting
vegetation types, heath and meadow, dominated by dwarf shrubs and herbaceous
plants respectively. This was done at each of three levels; across species,
within individual species, and the plant community using a community weighted
average approach. Several leaf and litter traits shifted with increasing
elevation in a manner consistent with greater conservation of nutrients at all
three levels, and the most consistent response was an increase in tissue N to P
ratio. However, litter decomposition was less directly responsive to elevation
because the leaf and litter traits which were most responsive to elevation were
not necessarily those responsible for driving decomposition. At the community
level, the response to elevation of foliar and litter traits, and
decomposability, varied greatly among the two vegetation types, highlighting the
importance of vegetation type in determining ecological responses to climatic
factors such as temperature. Finally our results highlight how understanding the
responses of leaf and litter characteristics of functionally distinct vegetation
types, and the processes that they drive, to temperature helps provide insights
about how future climate change could affect tundra ecosystems.
PMID- 22046444
TI - Chronic fluid flow is an environmental modifier of renal epithelial function.
AB - Although solitary or sensory cilia are present in most cells of the body and
their existence has been known since the sixties, very little is been known about
their functions. One suspected function is fluid flow sensing- physical bending
of cilia produces an influx of Ca(++), which can then result in a variety of
activated signaling pathways. Autosomal Dominant Polycystic Kidney Disease
(ADPKD) is a progressive disease, typically appearing in the 5(th) decade of life
and is one of the most common monogenetic inherited human diseases, affecting
approximately 600,000 people in the United States. Because ADPKD is a slowly
progressing disease, I asked how fluid flow may act, via the primary cilium, to
alter epithelial physiology during the course of cell turnover. I performed an
experiment to determine under what conditions fluid flow can result in a change
of function of renal epithelial tissue. A wildtype epithelial cell line derived
the cortical collecting duct of a heterozygous offspring of the Immortomouse
(Charles River Laboratory) was selected as our model system. Gentle orbital
shaking was used to induce physiologically relevant fluid flow, and periodic
measurements of the transepithelial Sodium current were performed. At the
conclusion of the experiment, mechanosensitive proteins of interest were
visualized by immunostaining. I found that fluid flow, in itself, modifies the
transepithelial sodium current, cell proliferation, and the actin cytoskeleton.
These results significantly impact the understanding of both the mechanosensation
function of primary cilia as well as the understanding of ADPKD disease
progression.
PMID- 22046445
TI - Cell-cell contact preserves cell viability via plakoglobin.
AB - Control over cell viability is a fundamental property underlying numerous
physiological processes. Cell spreading on a substrate was previously
demonstrated to be a major factor in determining the viability of individual
cells. In multicellular organisms, cell-cell contact is likely to play a
significant role in regulating cell vitality, but its function is easily masked
by cell-substrate interactions, thus remains incompletely characterized. In this
study, we show that suspended immortalized human keratinocyte sheets with
persisting intercellular contacts exhibited significant contraction, junctional
actin localization, and reinforcement of cell-cell adhesion strength. Further,
cells within these sheets remain viable, in contrast to trypsinized cells
suspended without either cell-cell or cell-substrate contact, which underwent
apoptosis at high rates. Suppression of plakoglobin weakened cell-cell adhesion
in cell sheets and suppressed apoptosis in suspended, trypsinized cells. These
results demonstrate that cell-cell contact may be a fundamental control mechanism
governing cell viability and that the junctional protein plakoglobin is a key
regulator of this process. Given the near-ubiquity of plakoglobin in
multicellular organisms, these findings could have significant implications for
understanding cell adhesion, modeling disease progression, developing
therapeutics and improving the viability of tissue engineering protocols.
PMID- 22046446
TI - Sedimentary environment influences the effect of an infaunal suspension feeding
bivalve on estuarine ecosystem function.
AB - The suspension feeding bivalve Austrovenus stutchburyi is a key species on
intertidal sandflats in New Zealand, affecting the appearance and functioning of
these systems, but is susceptible to several environmental stressors including
sedimentation. Previous studies into the effect of this species on ecosystem
function have been restricted in space and time, limiting our ability to infer
the effect of habitat change on functioning. We examined the effect of
Austrovenus on benthic primary production and nutrient dynamics at two sites, one
sandy, the other composed of muddy-sand to determine whether sedimentary
environment alters this key species' role. At each site we established large (16
m(2)) plots of two types, Austrovenus addition and removal. In winter and summer
we deployed light and dark benthic chambers to quantify oxygen and nutrient
fluxes and measured sediment denitrification enzyme activity to assess
denitrification potential. Rates of gross primary production (GPP) and ammonium
uptake were significantly increased when Austrovenus was added, relative to
removed, at the sandy site (GPP, 1.5 times greater in winter and summer; ammonium
uptake, 8 times greater in summer; 3-factor analysis of variance (ANOVA),
p<0.05). Denitrification potential was also elevated in Austrovenus addition
plots at the sandy site in summer (by 1.6 times, p<0.1). In contrast, there was
no effect of Austrovenus treatment on any of these variables at the muddy-sand
site, and overall rates tended to be lower at the muddy-sand site, relative to
the sandy site (e.g. GPP was 2.1 to 3.4 times lower in winter and summer,
respectively, p<0.001). Our results suggest that the positive effects of
Austrovenus on system productivity and denitrification potential is limited at a
muddy-sand site compared to a sandy site, and reveal the importance of
considering sedimentary environment when examining the effect of key species on
ecosystem function.
PMID- 22046447
TI - The mitochondrial genome of Baylisascaris procyonis.
AB - BACKGROUND: Baylisascaris procyonis (Nematoda: Ascaridida), an intestinal
nematode of raccoons, is emerging as an important helminthic zoonosis due to
serious or fatal larval migrans in animals and humans. Despite its significant
veterinary and public health impact, the epidemiology, molecular ecology and
population genetics of this parasite remain largely unexplored. Mitochondrial
(mt) genomes can provide a foundation for investigations in these areas and
assist in the diagnosis and control of B. procyonis. In this study, the first
complete mt genome sequence of B. procyonis was determined using a polymerase
chain reaction (PCR)-based primer-walking strategy. METHODOLOGY/PRINCIPAL
FINDINGS: The circular mt genome (14781 bp) of B. procyonis contained 12 protein
coding, 22 transfer RNA and 2 ribosomal RNA genes congruent with other
chromadorean nematodes. Interestingly, the B. procyonis mtDNA featured an
extremely long AT-rich region (1375 bp) and a high number of intergenic spacers
(17), making it unique compared with other secernentean nematodes characterized
to date. Additionally, the entire genome displayed notable levels of AT skew and
GC skew. Based on pairwise comparisons and sliding window analysis of mt genes
among the available 11 Ascaridida mtDNAs, new primer pairs were designed to
amplify specific short fragments of the genes cytb (548 bp fragment) and rrnL
(200 bp fragment) in the B. procyonis mtDNA, and tested as possible alternatives
to existing mt molecular beacons for Ascaridida. Finally, phylogenetic analysis
of mtDNAs provided novel estimates of the interrelationships of Baylisasaris and
Ascaridida. CONCLUSIONS/SIGNIFICANCE: The complete mt genome sequence of B.
procyonis sequenced here should contribute to molecular diagnostic methods,
epidemiological investigations and ecological studies of B. procyonis and other
related ascaridoids. The information will be important in refining the
phylogenetic relationships within the order Ascaridida and enriching the resource
of markers for systematic, population genetic and evolutionary biological studies
of parasitic nematodes of socio-economic importance.
PMID- 22046448
TI - Erythropoietin enhances nerve repair in anti-ganglioside antibody-mediated models
of immune neuropathy.
AB - Guillain-Barre syndrome (GBS) is a monophasic immune neuropathic disorder in
which a significant proportion of patients have incomplete recovery. The patients
with incomplete recovery almost always have some degree of failure of axon
regeneration and target reinnervation. Anti-ganglioside antibodies (Abs) are the
most commonly recognized autoimmune markers in all forms of GBS and specific Abs
are associated with the slow/poor recovery. We recently demonstrated that
specific anti-ganglioside Abs inhibit axonal regeneration and nerve repair in
preclinical models by activation of small GTPase RhoA and its downstream
effectors. The objective of this study was to determine whether erythropoietin
(EPO), a pleiotropic cytokine with neuroprotective and neurotrophic properties,
enhances nerve regeneration in preclinical cell culture and animal models of
autoimmune neuropathy/nerve repair generated with monoclonal and patient derived
Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were
used to assess the efficacy of EPO in reversing inhibitory effects of anti
ganglioside Abs on nerve repair. We found that EPO completely reversed the
inhibitory effects of anti-ganglioside Abs on axon regeneration in cell culture
models and significantly improved nerve regeneration/repair in an animal model.
Moreover, EPO-induced proregenerative effects in nerve cells are through EPO
receptors and Janus kinase 2/Signal transducer and activator of transcription 5
pathway and not via early direct modulation of small GTPase RhoA. These
preclinical studies indicate that EPO is a viable candidate drug to develop
further for neuroprotection and enhancing nerve repair in patients with GBS.
PMID- 22046449
TI - Temporal responses of wild-type pigmentation and RcaE-deficient strains of
Fremyella diplosiphon during light transitions.
AB - A temporal study was conducted to evaluate the dynamic complementary chromatic
adaptation (CCA) response of two Fremyella diplosiphon strains-wild-type
pigmentation strain SF33 and an RcaE-deficient (DeltarcaE) strain, which lacks
the photosensor that regulates CCA. SF33 and DeltarcaE cultures were monitored
for 15 days after transition of green-light (GL) acclimated cultures to red light
(RL) and vice versa. SF33 showed similar growth irrespective of the external
light quality; however, a DeltarcaE strain grew slower than SF33 under both RL
and GL. Chlorophyll a (chla) content increased in both strains over time and was
not much different under RL and GL indicating that chla biosynthesis is not
affected significantly by light quality or RcaE function. Phycoerythrin is the
sole pigment to absorb GL, whereas several pigments, i.e., allophycocyanin,
phycocyanin and chla, function under RL to drive photosynthesis. SF33 compensates
for this by synthesizing a higher percentage of PE under GL. The final pigment
distribution in the DeltarcaE mutant was found to be more different from SF33
under GL than under RL indicating that RcaE is needed for a transitional response
to RL and RL-dependent repression of PE accumulation, yet RcaE is virtually
critical for both transitioning to and a full adaptation to GL.
PMID- 22046450
TI - Nuclear actin: A key player in extracellular matrix-nucleus communication.
AB - Decades of research have shown that there is an intimate relationship between the
extracellular matrix (ECM) and cellular phenotype. While the existence of this
relationship remains inarguably clear, the exact details through which the
extracellular matrix controls phenotypic behavior at the gene expression level
are, for the most part, elusive. In a recent study on mammary epithelial cells,
nuclear actin was identified as a key effector protein through which laminin Type
III (LN1) attenuates RNA polymerase activity to promote growth arrest. This
finding forms the basis from which one can begin to envision a mechanism through
which the ECM can control nuclear function to enact changes in cell behavior.
Here I will briefly discuss the current depth of knowledge with regards to the
relationship between LN1 and nuclear actin and its implication in mammary
epithelial cell growth and function.
PMID- 22046451
TI - Regulation of neuronal functions by the E3-ubiquitinligase protein associated
with MYC (MYCBP2).
AB - The E3-ubiquitinligase MYCBP2 regulates neuronal growth, synaptogenesis and
synaptic plasticity by modulating several signaling pathways including the p38
MAPK signaling cascade. We found that loss of MYCBP2 in peripheral sensory
neurons inhibits the internalization of transient receptor potential vanilloid
receptor 1 (TRPV1) in a p38 MAPK-dependent manner. This prevented desensitization
of activity-induced calcium increases and prolongs formalin-induced thermal
hyperalgesia in mice. Besides its function in pain perception TRPV1 is also
involved in the regulation of neuronal growth. Therefore, the observed effect of
MYCBP2 on TRPV1 internalization could be part of the mechanisms underlying its
well documented regulatory role in neuronal growth. The clarification of the
mechanism is important for the understanding of the different MYCBP2-functions in
diverse neuronal subpopulations and species.
PMID- 22046452
TI - Can mathematics explain the evolution of human language?
AB - Investigation into the sequence structure of the genetic code by means of an
informatic approach is a real success story. The features of human language are
also the object of investigation within the realm of formal language theories.
They focus on the common rules of a universal grammar that lies behind all
languages and determine generation of syntactic structures. This universal
grammar is a depiction of material reality, i.e., the hidden logical order of
things and its relations determined by natural laws. Therefore mathematics is
viewed not only as an appropriate tool to investigate human language and genetic
code structures through computer science-based formal language theory but is
itself a depiction of material reality. This confusion between language as a
scientific tool to describe observations/experiences within cognitive constructed
models and formal language as a direct depiction of material reality occurs not
only in current approaches but was the central focus of the philosophy of science
debate in the twentieth century, with rather unexpected results. This article
recalls these results and their implications for more recent mathematical
approaches that also attempt to explain the evolution of human language.
PMID- 22046453
TI - Ion-selective self-referencing probes for measuring specific ion flux.
AB - The metal vibrating probe developed in the 1970s to measure electric current is
sensitive down to the micro-Amp range, but detects only net current due to flow
of multiple ions and is too large to measure from single cells.
Electrophysiological techniques which use glass microelectrodes such as voltage
clamping can be used on single cells but are also non-specific. Ion-selective
probes are glass microelectrodes containing at their tip a small amount of
ionophore permeable to a particular ion. The electrode is therefore sensitive to
changes in concentration of this ion. If the probe tip is moved at low frequency
between two points in a concentration gradient of this ion then the
electrochemical potential of the solution inside the electrode fluctuates in
proportion to the size of the ion gradient. This fluctuation is amplified and
recorded and is used to calculate the actual ion flux using Fick's law of
diffusion. In this mini-review we describe the technique of ion-selective self
referencing microelectrodes to measure specific ion fluxes. We discuss the
development of the technique and describe in detail the methodology and present
some representative results.
PMID- 22046454
TI - A tale of two sites: How ubiquitination of a G protein-coupled receptor is
coupled to its lysosomal trafficking from distinct receptor domains.
AB - The beta(2)-adrenergic receptor (beta(2)AR) is a prototypical G(s)-coupled
receptor belonging to the superfamily of seven transmembrane spanning
heptahelical receptors (7TMRs or G protein-coupled receptors [GPCRs])
therapeutically the most diverse and accessible class of cell surface receptors.
The classic pathway of beta(2)AR signaling (Fig. 1) is triggered by activation of
the heterotrimeric G protein G(s) by agonists (catecholamines-noradrenaline and
adrenaline). This in turn activates adenylyl cyclase leading to the generation of
second messenger signaling molecules (cyclic adenosine monophosphates, cAMP)
which subsequently activate protein kinase A (PKA) as well as some ion channels,
such as the class C type of L-type calcium channels, Ca(v)1.2.31 Here in we
review how trafficking and signaling of the beta(2)AR is regulated by the post
translational modification, ubiquitination.1.
PMID- 22046455
TI - Intraluminal volume homeostasis: A common sertonergic mechanism among diverse
epithelia.
AB - Volume homeostasis is a common physiological phenomenon for fluid secreting
organs, such as exocrine and endocrine glands. It is a manifestation of a finite
intraluminal space and an ever changing demand for secretory fluids. Volume
homeostasis addresses issues of fluid secretion, storage and clearance for
efficient functioning. Here we discuss the evidence gathered over the past 2-3
decades on serotonin's role as a feedback inhibitor of secretion in the mammary
gland, salivary gland, liver, pancreas, lung, thyroid gland and prostate gland.
We propose that serotonin action is a common mechanism of regulating intraductal
volume homeostasis.
PMID- 22046456
TI - DAAM family members leading a novel path into formin research.
AB - Formins are an important and evolutionarily well conserved class of actin binding
proteins with essential biological functions. Although their molecular roles in
actin regulation have been clearly demonstrated in vitro, their functions at the
cellular or organism levels are still poorly understood. To illustrate this
problem, but also to demonstrate potential ways forward, we focus here on the
DAAM group of formins. In vertebrates, DAAM group members have been demonstrated
to be important regulators of cellular and tissue morphogenesis but, as for all
formins, the molecular mechanisms underlying these morphogenetic functions remain
to be uncovered. The genome of the fruitfly Drosophila encodes a single DAAM gene
that is evolutionarily highly conserved. Recent work on dDAAM has already
provided a unique combination of observations and experimental opportunities
unrivalled by any other Drosophila formin. These comprise in vitro actin
polymerisation assays, subcellular studies in culture and in vivo, and a range of
developmental phenotypes revealing a role in tracheal morphogenesis, axonal
growth and muscle organization. At all these levels, future work on dDAAM will
capitalize on the power of fly genetics, raising unique opportunities to advance
our understanding of dDAAM at the systems level, with obvious implications for
other formins.
PMID- 22046458
TI - The yolk cell of the zebrafish blastula harbors functional apoptosis machinery.
AB - We recently described the implication of the Bcl-2 related antiapoptotic Nrz
protein during early zebrafish development. Nrz knock-down induces calcium
dependent cytoskeleton remodeling leading to margin constriction and premature
embryo lethality. In the YSL, nrz knock-down embryos exhibit some typical
features of apoptosis such as mitochondrial transmembrane potential loss and
cytochrome c release. However, downstream caspase-3 activation has not been
detected so far. Here, we report that the YSL contains fully functional apoptotic
machinery that can activate caspase-3 following zBax ectopic expression.
Furthermore, we present evidence that caspase-3 activation is actually detectable
in nrz knock-down embryos when premature margin constriction is prevented.
PMID- 22046457
TI - The diverse functions of short-term plasticity components in synaptic
computations.
AB - Short-term plasticity (STP) comprises several rapid synaptic processes that
operate on millisecond-to-minute timescales and modulate synaptic efficacy in an
activity-dependent manner. Facilitation and augmentation are two major STP
components in central synapses that work to enhance synaptic strength, while
various forms of short-term depression work to decrease it. These multiple
components of STP interact to perform a variety of synaptic computations. Using a
modeling approach in excitatory hippocampal synapses, we recently described the
contributions of individual STP components to synaptic operations. In this mini
review, we summarize the recent findings that revealed a wide palette of
functions that STP components play in neural operations and discuss their roles
in information processing, working memory and decision making.
PMID- 22046459
TI - Assembly and breakdown of microtubules within the midbody.
AB - In animal cells, cell division concludes with the separation of two daughter
cells during a process called cytokinesis. Abscission, the termination of
cytokinesis, is performed through formation of the midbody, a vis-a-vis
microtubule (MT)-rich structure bridging the daughter cells. Disassembly of the
midbody is the final stage of daughter cell separation and occurs in parallel to
membrane fusion in this area. To shed light on this process and to better
understand MT organization within the dense area of the midbody structure, an
integrative fluorescence microscopy and cryo-electron tomography (cryo-ET)
approach was taken.1 These efforts led to a resolving of MT architecture at
single-fiber resolution, resulting in a refined model of abscission.
PMID- 22046460
TI - Tao kinases as coordinators of actin and microtubule dynamics in developing
neurons.
AB - Drosophila tao, encoding a Ste20 family kinase, was identified as a gene involved
in ethanol, cocaine and nicotine sensitivity. The behavioral phenotypes appear to
be caused by defects in the development of the adult brain. Specifically,
Drosophila tao functions to promote axon guidance of mushroom body (MB) neurons.
The MB is a large structure in the central brain of the fly whose development and
function have been well characterized. tao interacts genetically with mutations
in the par-1 gene, also encoding a serine-threonine kinase. Since Par-1 has been
implicated in the regulation of microtubule dynamics, this suggests that tao
regulates the microtubule cytoskeleton in developing MB neurons. Here we discuss
these results in light of previous studies that have proposed that Drosophila tao
and its mammalian homologs function as a link between the actin and microtubule
cytoskeletons, regulating microtubule stability in response to actin signals.
PMID- 22046461
TI - FG repeats facilitate integral protein trafficking to the inner nuclear membrane.
AB - The mechanism for nucleo-cytoplasmic transport of integral membrane proteins is
poorly understood compared to transport of soluble molecules. We recently
demonstrated that at least four distinct mechanisms can contribute to transport
of integral proteins through the peripheral channels of the nuclear pore complex.
One of these requires having multiple phenylalanine-glycine (FG) pairings on the
integral protein. It also requires the nuclear pore complex protein Nup35, which
separately contains FG repeats. FG-repeats on nuclear pore complex proteins in
the central channel have been proposed to interact with FGs on transport
receptors to facilitate transport of soluble proteins. Here we show that FG
repeats occur quite frequently in both transmembrane and soluble proteins
identified in multiple separate proteomic analyses of nuclear envelopes. We
postulate that the FG repeats enable these proteins to function as their own
transport receptors.
PMID- 22046462
TI - How and why does Dia1 mRNA localize?
AB - Messenger RNA (mRNA) localization plays an important role in various cellular
functions. To date, two general mechanisms have been identified for intracellular
mRNA localization. The first one was identified by Blobel and colleagues more
than three decades ago, by which mRNAs encoding for membrane and secreted
proteins are targeted to the endoplasmic reticulum (ER) in a signal peptide
dependent manner.1 The second mechanism is for the intracellular targeting of
mRNAs encoding cytosolic proteins, which is dependent on specific sequence on the
mRNA called zipcode.2 Recently, we have identified a new mechanism which targets
Dia1 mRNA to the perinuclear ER in a zipcode-independent manner, even though the
mRNA encodes a cytosolic protein.3 Here, we provide an updated discussion on how
the Dia1 mRNA is targeted and what might be its physiological significance.
PMID- 22046463
TI - Physicochemical influence on odor hedonics: Where does it occur first?
AB - We recently reported data showing that, while human olfactory pleasantness is
modulated by semantic knowledge of smells, the physicochemical aspects of odorant
molecules are prominent determinants of odor hedonic valence, especially in
children and seniors, two age groups characterized by either low level of
(children) or weak access to (seniors) odor semantic knowledge.1 Here, we present
additional data from a human and an animal study, confirming that odorant
structure predicts odor pleasantness and suggesting that this influence may be
already engraved at receptor level.
PMID- 22046464
TI - Imaging functional neural circuits in zebrafish with a new GCaMP and the Gal4FF
UAS system.
AB - Measurement of the activity of neuronal ensembles is an essential step to
understand how the neuronal network is organized and functioning. Electrical
excitation of neurons causes calcium influx via voltage-gated calcium ion
channels, which can be monitored by calcium imaging using fluorescent calcium
probes. DNA-encoded calcium indicators (DECIs) such as cameleon and GCaMP have
been developed to specifically label a subpopulation of neurons. However, in many
cases, DECIs that had been developed and tested in vitro did not always show
expected performance in vivo. It is necessary to increase its sensitivity and
also to adjust its dynamic range to the physiological conditions. In our recent
study, we developed an improved version of GCaMP and tested its performance in
vivo using transgenic zebrafish. By combining the new GCaMP with targeted gene
expression via the Gal4FF-UAS system, we successfully imaged the activity of the
spinal motor circuit during spontaneous contractions of zebrafish larvae. Further
we report here that heptanol, a gap junction blocker, could alter the
spatiotemporal activation pattern of the motor circuit. Thus, we demonstrate that
calcium imaging with GCaMP is powerful to analyze neuronal activities under
normal and pharmacologically perturbed conditions.
PMID- 22046465
TI - Brain area specific regulation of synaptic AMPA receptors by phosphorylation.
AB - Regulation of synaptic AMPA receptors (AMPARs) is one of the key elements that
allow the nervous system to adapt to changes in the sensory environment as well
as for memory formation. One way to regulate AMPAR function is by reversible
changes in the phosphorylation of its subunits. We recently reported that
phosphorylation of the AMPAR subunit GluA1 (or GluR1) on serine-845 (S845) is a
pre-requisite step for sensory experience-dependent homeostatic synaptic
plasticity in the visual cortex. In particular, increasing GluA1-S845
phosphorylation upregulated cell surface and synaptic AMPAR levels. Here we
report that this is rather specific to the visual cortex, in that increasing
GluA1-S845 phosphorylation in hippocampal slices only increase cell surface
expression, but not synaptic AMPAR function. Our results suggest that depending
on the brain region divergent mechanisms may exist to regulate synaptic AMPAR
function with phosphorylation.
PMID- 22046466
TI - What are we measuring with GABA magnetic resonance spectroscopy?
AB - A number of recent papers1-3 have demonstrated a relationship between in vivo
concentration of GABA, as assessed using Magnetic Resonance Spectroscopy (MRS),
and an individual's task performance, giving a unique insight into the
relationship between physiology and behavior. However, interpretation of the
functional significance of the MRS GABA measure is not straightforward. Here we
discuss some of the outstanding questions as to how total concentration of GABA
within a cortical region relates to phasic and tonic GABA activity within the
cortical volume studied.
PMID- 22046467
TI - Emerging roles of phosphoinositide-specific phospholipases C in the ciliates
Tetrahymena and Paramecium.
AB - Phospholipases C (PLCs) that hydrolyze inositol phospholipids regulate vital
cellular functions in both eukaryotic and prokaryotic organisms. The PLC
superfamily consists of eukaryotic phosphoinositide-specific PLCs (PI-PLCs),
bacterial PLCs and trypanosomal PLCs.1 PI-PLCs hydrolyze phosphatidylinositol-4,5
bisphosphate (PtdIns4,5P(2)) to produce inositol-1,4,5-trisphosphate
(Ins1,4,5P(3)) and constitute a hallmark feature of eukaryotic cells. In metazoa,
this reaction is coupled to receptor signaling via specific PI-PLC isoforms and
results in acute increase of cytosolic Ca(2+) levels by Ins1,4,5P(3)-sensitive
Ca(2+) channels (IP(3)-receptors, IP3Rs).2 A striking result of many studies so
far has been the presence of a single PI-PLC gene in all unicellular eukaryotes
investigated, as opposed to expansion of PI-PLC isoforms in metazoa;3 this has
suggested that a single housekeeping PI-PLC represents an archetypal and
simplified form of PI-PLC signaling.3 Several studies however have noted a unique
expansion of PI-PLC/IP3R pathway components in ciliates.4,5 In a recent paper we
showed the presence of multiple functional PI-PLC genes in Tetrahymena
thermophila and biochemical characterization, pharmacological studies and study
of their expression patterns suggested that they are likely to serve distinct non
redundant roles.4 In this report we discuss these studies and how they advance
our understanding of PI-PLC functions in ciliates.
PMID- 22046468
TI - The regulation and role of neuronal gap junctions during development.
AB - Coupling of neurons by electrical synapses (gap junctions) transiently increases
in the mammalian CNS during development and plays a role in a number of
developmental events, including neuronal death. The coupling subsequently
decreases and remains low in the adult, confined to specific subsets of neurons.
In a recent study we have demonstrated that the developmental increase in
neuronal gap junction coupling is regulated by the balance between the activity
of two neurotransmitter receptors, group II metabotropic glutamate receptors
(mGluR) and GABA(A) receptors. Specifically, we found that activation of group II
mGluRs induces the developmental increases in neuronal gap junction coupling and
expression of connexin 36 (Cx36; neuronal gap junction protein) and activation of
GABA(A) receptors counteracts to these increases. We also established that the
regulation by both neurotransmitter receptors is via a neuron-restrictive
silencer element in the Cx36 gene promoter and the 3'-untranslated region of the
Cx36 mRNA. Importantly, we demonstrated that mechanisms for the developmental
increase in neuronal gap junction coupling directly control the death/survival
mechanisms in developing neurons.
PMID- 22046469
TI - Nuclear actin and transcriptional activation.
AB - Differentiated cells do not revert to an embryonic state in normal development.
However, the method called nuclear reprogramming enables these differentiated
cells to be reversed to an embryonic state. One essential event in the
reprogramming process is reactivation of embryonic genes such as Oct4 (also known
as Pou5f1). This reprogramming of transcriptional programs can be achieved by
transplantation of mammalian somatic nuclei to the giant Xenopus laevis oocyte
nucleus, referred to as the germinal vesicle (GV). Factors and mechanisms
responsible for this transcriptional reprogramming have not been elucidated.
Recently, we have found that a polymerized form of actin is abundantly present in
nuclei transplanted into the Xenopus oocyte nucleus and plays an important role
in transcriptional reactivation of Oct4. This study emphasizes a significant
contribution of nuclear actin in transcriptional activation. Here, we discuss
possible roles of nuclear actin in Xenopus oocytes and in other cell types in the
context of transcriptional activation.
PMID- 22046470
TI - Nitric oxide regulates non-classical secretion of tissue transglutaminase.
AB - Nitric oxide (NO) is an endogenous second messenger which acts as a potent
vasodilator, anti-inflammatory, anti-thrombotic and pro-angiogenic agent in the
vasculature. Recent studies revealed that the effects of NO on blood vessels are
mediated in part by its ability to regulate protein trafficking machinery and
vesicle-based exocytosis in vascular cells. Specifically, NO-dependent S
nitrosylation of N-ethylmaleimide sensitive factor (NSF), an ATPase that enables
membrane fusion, was shown to inhibit exocytosis of vesicular secretory
compartments such as endothelial Weibel-Palade bodies, platelet alpha granules
and cytolytic granules from activated lymphocytes. Tissue transglutaminase (tTG
or TG2) is a multifunctional protein synthesized and secreted by various cell
types in the vasculature, which is involved in multiple vascular diseases,
including atherosclerosis, vascular calcification and age-dependent aortic
stiffening. Our recent findings indicate that tTG is delivered to the cell
surface and the extracellular matrix (ECM) via a non-classical ER/Golgi
independent secretion pathway, which depends on the recycling endosomes and the
NSF function. Here we report that NO attenuates the unconventional secretion of
tTG in human aortic endothelial cells. NO-dependent downregulation of
extracellular tTG levels via inhibition of its secretion might be a part of
general physiological mechanism which limits externalization of adhesive, pro
inflammatory and thrombogenic proteins in the vasculature.
PMID- 22046471
TI - Cell entry and exit by periodontal pathogen via recycling pathway.
AB - In the oral cavity, gingival epithelial cell (GEC) layers function as an innate
host defense system to prevent intrusion by periodontal bacteria. Nevertheless,
Porphyromonas gingivalis, the most well-known periodontal pathogen, can enter
GECs and pass through the epithelial barrier into deeper tissues. An
intracellular location is considered advantageous for bacteria to escape from
immune surveillance by the host as well as antibiotic pressure, leading to
intracellular persistence, multiplication and dissemination to adjacent tissues.
P. gingivalis are invaginated by gingival epithelial cells via the endocytic
pathway, and some intracellular bacteria are sorted to lytic compartments,
including autolysosomes and late endosomes/lysosomes, while a considerable number
of the remaining organisms are sorted to Rab11- and RalA-positive recycling
endosomes, followed by bacterial exit from the cells. Exited bacteria can re
enter fresh cells. However, dominant negative forms and RNAi-knockdown of Rab11,
RalA and exocyst complex subunits (Sec5, Sec6 and Exo84) significantly disturb
the exit of P. gingivalis. These are the first known results to show that the
endocytic recycling pathway mediates bacterial exit from infected cells to
neighboring cells and may provide important information regarding the exit
mechanisms of various invasive pathogens.
PMID- 22046472
TI - Golgi-associated Rab14, a new regulator for Chlamydia trachomatis infection
outcome.
AB - Chlamydia trachomatis is the causing agent of the most frequent bacterial
sexually-transmitted diseases worldwide and is an underlying cause of chronic
pelvic inflammatory diseases and cervical cancer. It is an obligate intracellular
bacterium that establishes a close relationship with the Golgi complex and
parasites the biosynthetic machinery of host cells. In a recent study, we have
demonstrated that Rab14, a newly-described Golgi-associated Rab, is involved in
the delivery of sphingolipids to the growing bacteria-containing vacuole. The
interference with Rab14-controlled trafficking pathways delays chlamydial
inclusion enlargement, decreases bacterial lipid uptake, negatively impact on
bacterial differentiation, and reduces bacterial progeny and infectivity. C.
trachomatis manipulation of host trafficking pathways for the acquisition of
endogenously-biosynthesized nutrients arises as one of the characteristics of
this highly evolved pathogen. The development of therapeutic strategies targeted
to interfere with bacterium-host cell interaction is a new challenge for
pharmacological approaches to control chlamydial infections.
PMID- 22046473
TI - To bee or not to bee, this is the question...: The inborn numerical competence of
humans and honeybees.
AB - Human inborn numerical competence means our ability to recognize object numbers
precisely under circumstances which do not allow sequential counting. This
archaic process has been called "subitizing," from the Latin "subito" = suddenly,
immediately, indicating that the objects in question are presented to test
persons only for a fraction of a second in order to prevent counting. In
contrast, however, sequential counting, an outstanding cultural achievement of
mankind, means to count "1, 2, 3, 4, 5, 6, 7, 8..." without a limit. The
following essay will explain how the limit of numerical competence, i.e., the
recognition of object numbers without counting, has been determined for humans
and how this has been achieved for the first time in case of an invertebrate, the
honeybee. Finally, a hypothesis explaining the influence of our limited, inborn
numerical competence on counting in our times, e.g., in the Russian language,
will be presented. Subitizing versus counting by young Down syndrome infants and
autistics and the Savant syndrome will be discussed.
PMID- 22046474
TI - Ophiocordyceps unilateralis: A keystone species for unraveling ecosystem
functioning and biodiversity of fungi in tropical forests?
AB - Ophiocordyceps unilateralis (Ascomycota: Hypocreales) is a specialized parasite
that infects, manipulates and kills formicine ants, predominantly in tropical
forest ecosystems. We have reported previously, based on a preliminary study in
remnant Atlantic Forest in Minas Gerais (Brazil), that O. unilateralis represents
a species complex. On each of the four species of infected carpenter ant
(Camponotus) collected, the fungus-characterized macroscopically by a single
stalk arising from the dorsal neck region on which the sexual structures
(stromatal plates) are borne laterally-can readily be distinguished both
microscopically and functionally. Here, we describe and discuss the biology, life
cycle and infection strategies of O. unilateralis s.l. and hypothesize that there
may be hundreds of species within the complex parasitizing formicine ants
worldwide. We then address the diversity within related hypocrealean fungi, with
particular reference to symbionts (mutualists through to parasites), and argue
that the widely-quoted total of extant fungi (1.5 million species) may be grossly
underestimated.
PMID- 22046475
TI - Heterogeneous release probabilities and activity-dependent short-term synaptic
depression.
AB - Synaptic transmission is a major mechanism by which neurons communicate with each
other. Basic steps in neurotransmitter release are similar in all synapses.
However, many properties of release vary between synapses and reflect specific
structural and functional requirements, endowing synapses with specialized
functions. Recently, Gelman et al.1 described properties of release and short
term depression at specialized nicotinic synapses in the brainstem of goldfish,
Carassius auratus (Linnaeus). These axo-axonic synapses between the Mauthner cell
collaterals and their targets, cranial relay neurons (CRNs), exhibit strong short
term depression, even at stimulation frequencies as low as 0.33 Hz. In short,
amplitudes of post-synaptic responses, evoked by presynaptic trains of action
potentials, were depressed with a time course approximated by a sum of two
exponential functions. Initially, fast depression reduced the amplitude of
EPSP(2) (response after the second stimulus), to less than 50% of EPSP(1)
(response after the first stimulus). This was followed by a slow component of
depression that produced an additional 10-30% amplitude reduction over a time
span of tens to hundreds of seconds. Interestingly, depressed EPSPs exhibited
longer latencies than that of the "undepressed" EPSP1. Additionally, fast and
slow calcium chelators (BAPTA and EGTA), injected pre-synaptically, were equally
potent in reducing release. These data are consistent with a previously proposed
general mechanism that assumes a change in release probability after the initial
release. However, in an alternative interpretation the results could be
coherently explained by postulating two releasable pools of vesicles, with high
and low release probabilities, and a generally accepted depletion scheme. This
latter interpretation will be discussed in this article.
PMID- 22046476
TI - ESCRT or endosomes?: Tales of the separation of two daughter cells.
AB - The final abscission event of cytokinesis is necessary for daughter cells to part
ways from one another. Failure to properly divide has been indicated as a
potential cancer initiating event due to an increase in cellular aneuploidy.
However, the exact mechanisms of abscission have remained obscured by our
inability to properly discern the spatiotemporal regulation of the various
proteins and organelles required for cytokinesis. Three recent publications have
taken slightly varied high resolution imaging approaches to visualize cytokinesis
and abscission. As a result of this work, two differing, but not necessarily
mutually exclusive, models have emerged. One model is ESCRT-dependent and the
other, recycling endosome-dependent, each describing the steps leading up to the
final abscission event. Presently these models describe late cytokinesis events
leading to abscission in greater detail than previously known.
PMID- 22046477
TI - Can alternative pathways mediate the influence of queen number on nestmate
discrimination in ants?
AB - The evolution of social life is usually associated with capabilities of
individuals to protect group boundaries against foreign individuals. In colonies
of ants, the number of reproductive queens is known to influence the accuracy of
nestmate discrimination by resident workers. However, the pathway by which this
effect is mediated remains unclear. The major hypothesis has long been that
workers from multiple-queen colonies commit more discrimination errors against
foreigners because their colonies contain a broader diversity of genetically
determined cues characterising colony membership. Until recently, this hypothesis
has received little attention and poor empirical support. In a recent study,
Meunier et al.1 proposed an alternative, albeit not mutually exclusive
hypothesis. The presence of one or multiple queens modifies chemical signals on
colony members that trigger aggressive or cooperative behaviors during foreign
encounters. Here, I detail how this new hypothesis is congruent with previous
results and discuss potential limits and evolutionary implications of the two
suggested hypotheses.
PMID- 22046478
TI - Homeostasis of the Drosophila adult retina by actin-capping protein and the Hippo
pathway.
AB - The conserved Hippo signaling pathway regulates multiple cellular events,
including tissue growth, cell fate decision and neuronal homeostasis. While the
core Hippo kinase module appears to mediate all the effects of the pathway,
various upstream inputs have been identified depending on tissue context. We have
recently shown that, in the Drosophila wing imaginal disc, actin-Capping Protein
and Hippo pathway activities inhibit F-actin accumulation. In turn, the reduction
in F-actin sustains Hippo pathway activity, preventing Yorkie nuclear
translocation and the upregulation of proliferation and survival genes. Here, we
investigate the role of Capping Protein in growth-unrelated events controlled by
the Hippo pathway. We provide evidence that loss of Capping Protein induces
degeneration of the adult Drosophila retina through misregulation of the Hippo
pathway. We propose a model by which F-actin dynamics might be involved in all
processes that require the activity of the core Hippo kinase module.
PMID- 22046479
TI - The role of the membrane confinement in the surface area regulation of cells.
AB - We propose a new in vitro system to study the mechanics of surface area
regulation in cells, which takes into an account the spatial confinement of the
cell membrane. By coupling a lipid bilayer to the strain-controlled deformation
of an elastic sheet, we show that upon straining the supported lipid bilayer
expands its surface area by absorbing adherent lipid vesicles and upon
compression decreases its area by expelling lipid tubes out of its plane. The
processes are reversible and closely resemble in vivo observations on shrinking
cells. Our results suggest that the mechanics of the area regulation in cells is
controlled primarily by the membrane tension and the effects of the membrane
confinement.
PMID- 22046480
TI - Evolutionary variations of VPS29, and their implications for the heteropentameric
model of retromer.
AB - The retromer complex is conserved across all eukaryotic species and functions in
physiologically important sorting processes at the endosomal membrane. A key
component of retromer is the VPS29 protein that, although structurally similar to
phospho-diesterases, has been convincingly shown in the recent study by Swarbrick
et al. (PLoS One 6:e20420, 2011) to be a rigid scaffold that interacts with
various proteins that function with retromer in endosomal protein sorting. A
widely held view, based on initial observations in Saccharomyces cerevisiae, is
that retromer functions as a stable heteropentamer. This is, however, contrary to
experimental data presented in Swarbrick et al. (and in other studies) that
indicate that retromer in higher eukaryotes is a looser association of two
subcomplexes that respectively mediate cargo-selection and membrane tubulation.
Here we present an analysis of evolutionary variation of the VPS29 protein and
discuss why the retromer complex as first characterized in S. cerevisiae is not
representative of retromer in other eukaryotic taxa.
PMID- 22046481
TI - Cytoplasmic to nuclear localization of fatty-acid binding protein correlates with
specific forms of long-term memory in Drosophila.
AB - We recently reported evidence implicating fatty-acid binding protein (Fabp) in
the control of sleep and memory formation. We used Drosophila melanogaster to
examine the relationship between sleep and memory through transgenic
overexpression of mouse brain-Fabp, Fabp7, or the Drosophila Fabp homolog,
(dFabp). The key findings are that 1) a genetically induced increase in daytime
consolidated sleep (naps) correlates with an increase in cognitive performance,
and 2) a late "window" of memory consolidation occurs days after the
traditionally understood "synaptic" consolidation. Exactly how Fabp-signaling may
be involved in converting normal to enhanced long-term memory (LTM) is not known.
Here we describe additional data which support relative subcellular compartmental
localization of Fabp in regulating stage associations of different forms of
memory in Drosophila. Anesthesia resistant memory (ARM) is a longer lasting
memory that is produced by massed training, but unlike LTM produced by spaced
training, it is insensitive to protein synthesis inhibitors and does not persist
as long. We observed that the ratio of ARM to LTM performance index of Fabp7
transgenic flies is proportional to the relative cytoplasmic to nuclear Fabp7
expression level. These data suggest a common lipid-signaling cascade exists
between phases of memory formation previously thought to be molecularly distinct.
PMID- 22046482
TI - The evolution and role of mitochondrial fusion and fission in aging and disease.
AB - Mitochondria contain their own genetic material and evolved from prokaryotic
ancestors some two billion years ago. They are the main source of the cell's
energy supply and are involved in such important processes as apoptosis,
mitochondrial diseases and aging. Mitochondria display a complex dynamical
behavior involving cycles of fusion and fission, the function of which is as yet
unknown. We recently proposed a concise theory that explains: (1) why fusion and
fission have evolved, (2) how these processes relate to the accumulation of
mitochondrial mutants during aging and (3) why mtDNA is located close to the
respiration complexes where most radicals are generated. We also believe that
this 'organelle control' theory may explain why mutations in mitochondrial tRNA
genes are the most prevalent kind of defect associated with inherited human
mitochondrial diseases, despite the fact that mt-tRNA genes account for only 5%
of the mtDNA coding sequence.
PMID- 22046483
TI - Strategies to harness immunity against infectious pathogens after haploidentical
stem cell transplantation.
AB - Viral and fungal infections account for significant morbidity and mortality,
particularly in pediatric patients with profound immune suppression resulting
from allogeneic hematopoietic stem cell transplantation (HSCT). Therapies with
anti-viral and anti-fungal drugs are often associated with significant toxicity,
are of limited efficacy and can induce drug resistance. One innovative approach
to prevent and/or treat viral and fungal infections involves the adoptive
transfer of in vitro-expanded or in vitro-generated pathogen-specific T cells.
This review summarizes the clinical trials that have been run to date with virus-
and fungus-specific T cells, with special emphasis on the clinical context of
haploidentical HSCT for pediatric malignancies. It will also discuss initiatives
and strategies to overcome the hurdles associated with time-consuming and complex
GMP-grade laboratory procedures required to generate pathogen-specific T cells.
PMID- 22046484
TI - Translational research: current status, challenges and future strategies.
AB - Advances in translational research are expected to mitigate the recent drought in
new drug development. Despite significant progress recently made in biological
sciences, the results are decidedly mixed with significant breakthrough in some
disease areas while extensive work remains to be completed in other areas. This
review article provides a general survey of the current landscape of
translational research so as to identify progress and areas of needs and the
associated strategy. While significant advances in the development of
translational tools have been made in all fronts, the availability of predictive
preclinical models remains critical for the success of translational research.
This is directly correlated with the success of translational research as
illustrated by the recent approval of targeted drug therapies. By the same logic,
unexpected side effects can also be explained by laboratory findings, thus
completing the translational cycle. Because of this reason, further collaboration
between preclinical and clinical scientists is essential. Non-scientific issues
have important influence on the future of this endeavor cannot be underestimated
either. Nonetheless, with definitive commitment of private industry and public
resources, the future of translational research is promising.
PMID- 22046485
TI - Emerging drug discovery approaches for selective targeting of "precursor"
metastatic breast cancer cells: highlights and perspectives.
AB - Breast cancer is a prevalent disease and a major cause of morbidity and cancer
related deaths among women worldwide. A significant number of patients at the
time of primary diagnosis present metastatic disease, at least to locoregional
lymph nodes, which results in somewhat unpredictable prognosis that often prompts
adjuvant systemic therapies of various kinds. The time course of distant
recurrence is also unpredictable with some patients sustaining a recurrence
within months after diagnosis, even during adjuvant treatments, while others can
experience recurrence years or decades after initial diagnosis. To date,
clinically approved therapeutics yielded marginal benefits for patients with
systemic metastatic breast disease, since despite high clinical responses to
various therapies, the patients virtually always become resistant and tumor
relapses. Molecular profiling studies established that breast cancer is highly
heterogeneous and encompasses diverse histological and molecular subtypes with
distinct biological and clinical implications in particular in relation to the
incidence of progression to metastasis. The latter has been recognized to result
from late genetic events during the multistep progression proposed by the
dominant theory of carcinogenesis. However, there is evidence that the
dissemination of primary cancer can also be initiated at a very early stage of
cancer development, originating from rare cell variants, possibly cancer stem
like cells (CSC), with invasive potential. These precursor metastatic cancer
cells with stem-like properties are defined by their ability to self-renew and to
regenerate cell variants, which have high plasticity and intrinsic invasive
properties required for dissemination and tropism toward specific organs. Equally
relevant to the CSC hypothesis for metastasis formation is the epithelial
mesenchymal transition (EMT) process, which is critical for the acquisition of
cancer cell invasive behavior and for selection/gain of CSC properties. These
exciting concepts have led to the formulation of various approaches for targeting
precursor metastatic cells, and these have taken on greater priority in
therapeutic drug discovery research by both academia and pharmaceuticals. In this
review, we focus on current efforts in medicinal chemistry to develop small
molecules able to target precursor metastatic cells via interference with the
CSC/EMT differentiation program, self-renewal, and survival. It is not meant to
be comprehensive and the reader is referred to selected reviews that provide
coverage of related basic aspects. Rather, emphasis is given to promising
molecules with CSC/EMT signaling at the preclinical stage and in clinical trials
that are paving the way to new generations of anti-metastasis drugs.
PMID- 22046486
TI - The clinical value of von Willebrand factor in colorectal carcinomas.
AB - BACKGROUND: To identify the value of von Willebrand factor (vWF) as a clinical
marker in colorectal carcinoma (CRC). METHODS: Plasma levels of vWF were measured
in 79 patients with UICC Stage I-IV CRC at time of operation and correlated with
TNM categories, levels of the carcinoembryonic antigen (CEA), blood groups (BG)
and 19 controls (CO). CO included cancer-free patients without bacterial or viral
infections. For tissue analysis paraffin embedded tumour and mucosa sections of
operation specimens were stained immunohistochemically for vWF and compared to
vWF plasma levels as well as to TNM categories. RESULTS: VWF plasma levels in CRC
patients were significantly dependent on blood groups (p=0.012) and elevated
compared to the normal ranges as well as to controls (BG 0: p=0.668, BG A/AB/B:
p=0.020). CRC-Patients over 60 years of age presented with significantly higher
vWF levels than patients below 60 years (BG 0: p=0.005; BG A/AB/B: p=0.035).
There was no correlation of vWF plasma levels and UICC stages in CRC. Patients
with elevated vWF plasma levels also presented with elevated CEA levels, but
significance was missing (p=0.080). VWF concentration within the tumour tissue
was independent of concentration within normal mucosa, blood groups,
histopathological characteristics and did not correlate with plasma vWF levels.
CONCLUSION: VWF plasma levels are elevated in CRC patients, but not in a stage
dependent manner. Besides the tumour at least blood groups and age mainly
influence plasma vWF levels. In our opinion vWF as a routinely used clinical
marker in CRC cannot be recommended.
PMID- 22046487
TI - Potential non-oncological applications of histone deacetylase inhibitors.
AB - Histone deacetylase inhibitors have emerged as a new class of anticancer
therapeutic drugs. Their clinical utility in oncology stems from their intrinsic
cytotoxic properties and combinatorial effects with other conventional cancer
therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic
acid (Vorinostat, Zolinza(r)) and depsipeptide (Romidepsin, Istodax(r)) have been
approved by the US Food and Drug Administration for the treatment of refractory
cutaneous T-cell lymphoma. Further, there are currently over 100 clinical trials
involving the use of histone deacetylase inhibitors in a wide range of solid and
hematological malignancies. The therapeutic potential of histone deacetylase
inhibitors has also been investigated for numerous other diseases. For example,
the cytotoxic properties of histone deacetylase inhibitors are currently being
harnessed as a potential treatment for malaria, whereas the efficacy of these
compounds for HIV relies on de-silencing latent virus. The anti-inflammatory
properties of histone deacetylase inhibitors are the predominant mechanisms for
other diseases, such as hepatitis, systemic lupus erythematosus and a wide range
of neurodegenerative conditions. Additionally, histone deacetylase inhibitors
have been shown to be efficacious in animal models of cardiac hypertrophy and
asthma. Broad-spectrum histone deacetylase inhibitors are clinically available
and have been used almost exclusively in preclinical systems to date. However, it
is emerging that class- or isoform-specific compounds, which are becoming more
readily available, may be more efficacious particularly for non-oncological
applications. The aim of this review is to provide an overview of the effects and
clinical potential of histone deacetylase inhibitors in various diseases. Apart
from applications in oncology, the discussion is focused on the potential
efficacy of histone deacetylase inhibitors for the treatment of neurodegenerative
diseases, cardiac hypertrophy and asthma.
PMID- 22046488
TI - LAT1 expression is closely associated with hypoxic markers and mTOR in resected
non-small cell lung cancer.
AB - AIM: L-type amino acid transporter 1 (LAT1) is known to be highly expressed in
various human neoplasms. However, little is known about how LAT1 is associated
with glucose metabolism, hypoxia and mammalian target of rapamycin (mTOR)
signaling pathway in non-small cell lung cancer (NSCLC). The aim of this study is
to evaluate the relationship between LAT1 expression, and hypoxic marker and mTOR
pathway in resected NSCLC. METHODS: One hundred and sixty patients were included
in this study. Tumors sections were stained by immunohistochemistry for LAT1,
glucose transporter 1 (Glut1), hypoxia inducible factor-1alpha (HIF-1alpha),
hexokinase I, vascular endothelial growth factor (VEGF), microvessel density
(MVD) by determinate by CD34, epidermal growth factor receptor (EGFR),
Phosphatase and tensin analog (PTEN), phosph-Akt, phosph-mTOR and phosph-S6K.
RESULTS: A positive LAT1 and CD98 expression were recognized in 36.8% (59/160)
and 33.7% (54/160), respectively (p=0.640). LAT1 expression was significantly
associated with CD98, hypoxic markers (Glut1, HIF-1alpha, hexokinase I, VEGF and
CD34) and mTOR pathway (EGFR, a loss of PTEN, p-mTOR and p-S6K), especially in
lung adenocarcinoma (AC). The expression profile of these biomarkers was
significantly higher in non-AC than in AC, but almost these biomarkers were
equally expressed between AC (n=16) and non-AC (n=43) patients with a positive
LAT1 expression. Overexpression of LAT1 was closely associated with poor outcome
in patient with AC. CONCLUSION: LAT1 expression is closely correlated with
hypoxic markers and mTOR pathway in patients with resected NSCLC.
PMID- 22046489
TI - The gold (III) porphyrin complex, gold-2a, suppresses WNT1 expression in breast
cancer cells by enhancing the promoter association of YY1.
AB - The gold (III) porphyrin complex, gold-2a, elicits anti-tumor activity by
targeting the Wnt/beta-catenin signaling pathway [Chow KH et al, Cancer Research
2010;70(1):329-37]. Here, the molecular mechanisms underlying the inhibitory
effects of this compound on WNT1 gene expression were elucidated further. A
response element to gold-2a was identified located within the -1290 to -1112 nt
region of the WNT1 promoter, containing a binding site for the transcription
regulator Yin Yang 1 (YY1). Gold-2a promoted the association of YY1 and
suppressor of zeste 12 (Suz12; a component of the polycomb repressor complex 2)
with the WNT1 promoter. Under normal culture conditions, the intracellular
translocalization of YY1 was synchronized with cell cycle progression and WNT1
expression. Gold-2a promoted the nuclear accumulation and abolished the nuclear
exportation of YY1, resulting in a persistent inhibition of WNT1 expression and a
cell cycle arrest at G1/S phase. A dimorphic role of YY1 in regulating cell
proliferation and division was revealed. Thus, the present study extends the
understanding of the anti-tumor mechanism of gold-2a to the epigenetic level,
which involves the modulation of the dynamic interactions between YY1 and a
specific region of the WNT1 promoter.
PMID- 22046491
TI - TTF-1 positive small cell cancers: Don't think they're always primary pulmonary!
AB - Thyroid transcription factor 1 (TTF-1) plays a key role in morphogenesis of the
lungs and is expressed in up to 90% of pulmonary small cell carcinomas. This
explains why this marker is frequently used in the search for the primary origin
of metastatic endocrine tumours. Here we report on a TTF-1 expressing mixed
endocrine-exocrine carcinoma of the common bile duct in a patient with pulmonary
nodules that did not appear to be neoplastic. TTF-1 positivity in pulmonary and
extrapulmonary neuroendocrine tumours is reviewed, and we conclude that TTF-1
expression in neuroendocrine tumours of the small-cell type are not uncommon at
extrapulmonary locations. Therefore, immunohistochemistry for TTF-1 in such
tumours should be interpreted with caution.
PMID- 22046490
TI - Current status of robot-assisted gastric surgery.
AB - In an effort to minimize the limitations of laparoscopy, a robotic surgery system
was introduced, but its role for gastric cancer is still unclear. The objective
of this article is to assess the current status of robotic surgery for gastric
cancer and to predict future prospects. Although the current study was limited by
its small number of patients and retrospective nature, robot-assisted gastrectomy
with lymphadenectomy for the treatment of gastric cancer is a feasible and safe
procedure for experienced laparoscopic surgeons. Most studies have reported
satisfactory results for postoperative short-term coutcomes, such as:
postoperative oral feeding, gas out, hospital stay and complications, compared
with laparoscopic surgery; the difference is a longer operation time. However,
robotic surgery showed a shallow learning curve compared with the familarity of
conventional open surgery; after the accumulation of several cases, robotic
surgery could be expected to result in a similar operation time. Robotic-assisted
gastrectomy can expand the indications of minimally invasive surgery to include
advanced gastric cancer by improving the ability to perform lymphadenectomy.
Moreover, "total" robotic gastrectomy can be facilitated using a robot-sewing
technique and gastric submucosal tumors near the gastroesophageal junction or
pylorus can be resected safely by this novel technique. In conclusion, robot
assisted gastrectomy may offer a good alternative to conventional open or
laparoscopic surgery for gastric cancer, provided that long-term oncologic
outcomes can be confirmed.
PMID- 22046492
TI - Primary hepatic leiomyosarcoma: Case report and literature review.
AB - Primary hepatic leiomyosarcoma are rare tumors with less than 30 cases reported
in the English literature. Non specific presentations and often diagnosis delayed
until they reach a large size, is the norm with therapy leading to an often
dismal prognosis. A 67-year-old man presented complaining of abdominal pain and a
palpable abdominal mass since Jan 2010. Abdominal ultrasonography and abdominal
computed tomography revealed a large tumor in the left lobe of the liver.
Surgical exploration was undertaken and an extended left hepatectomy with
extension onto the dorsal part of segment 8 preserving the MHV with partial
resection of segment 6 was undertaken. The weight of the resected specimen was
1300 g of the left lobectomy specimen and 8 g of the segment 6 partial resection
specimen. The pathology report confirmed the diagnosis of leiomyosarcoma. On
immunohistochemistry, the tumor cells were positive for smooth muscle actin
stain. The patient is on regular follow up and is currently 9 mo post resection
with no evidence of recurrence. We report the case of a resected primary hepatic
leiomyosarcoma and emphasize the need for a global database for these rare tumors
to promote a better and broader understanding of this less understood subject.
PMID- 22046494
TI - Misinformation increases symptom reporting: a test - retest study.
AB - OBJECTIVES: We examined whether misleading information (i.e. misinformation) may
promote symptom reporting in non-clinical participants. DESIGN: A test-retest
study in which we collected baseline data about participants' psychological
symptoms and then misinformed them that they had rated two target symptoms
relatively highly. During an interview, we determined whether participants would
notice this misinformation and at direct and one-week follow-up, we evaluated
whether the misinformation would exacerbate retest measures of the same symptoms.
SETTING: A psychological laboratory. PARTICIPANTS: A total of 78 undergraduate
students. MAIN OUTCOME MEASURES: Participants' scores on a widely used self
report measure of psychological symptoms. RESULTS: We found that most
participants (63%) were blind to the discrepancies between their original symptom
ratings and the upgraded scores they were misinformed with. Furthermore, at the
one-week follow-up retest, blind participants revised their symptom ratings in
the direction of the misinformation (i.e. they increased their ratings of these
symptoms). CONCLUSION: Introspective monitoring of common psychological symptoms
is poor and this creates an opportunity for misinformation and symptom
escalation. Our finding bears relevance to theories about the iatrogenic
amplification of medically unexplained symptoms.
PMID- 22046493
TI - Exploiting the P-1 pocket of BRCT domains toward a structure guided inhibitor
design.
AB - Breast cancer gene 1 carboxy terminus (BRCT) domains are found in a number of
proteins that are important for DNA damage response (DDR). The BRCT domains bind
phosphorylated proteins and these protein-protein interactions are essential for
DDR and DNA repair. High affinity domain specific inhibitors are needed to
facilitate the dissection of the protein-protein interactions in the DDR
signaling. The BRCT domains of BRCA1 bind phosphorylated protein through a pSXXF
consensus recognition motif. We identified a hydrophobic pocket at the P-1
position of the pSXXF binding site. Here we conducted a structure-guided
synthesis of peptide analogs with hydrophobic functional groups at the P-1
position. Evaluation of these led to the identification of a peptide mimic 15
with a inhibitory constant (K(i)) of 40 nM for BRCT(BRCA1). Analysis of the
TopBP1 and MDC1 BRCT domains suggests a similar approach is viable to design high
affinity inhibitors.
PMID- 22046495
TI - Patient and provider delays in breast cancer patients attending a tertiary care
centre: a prospective study.
AB - OBJECTIVES: To find out factors that are responsible for the patient or provider
delays in the diagnosis of breast cancer in India. DESIGN: This prospective study
was designed to be conducted over a period of two years including a cohort of 100
patients with locally advanced breast cancer. The delays were assessed using
questionnaires prepared according to the Indian scenario. SETTING: A prospective
study in an Indian setting. PARTICIPANTS: One hundred patients with locally
advanced breast cancer receiving neoadjuvant chemotherapy were included after
providing informed consent and receiving ethical committee clearance. MAIN
OUTCOME MEASURES: The most common factor responsible for delays in diagnosis was
observed to be the health providers, although illiteracy and lack of adequate
healthcare services also contributed significantly. Unregistered medical
practitioners or quacks contributed significantly to the delays in reporting and
diagnosis of the disease. RESULTS: One hundred patients of locally advanced
breast cancer were evaluated using standardized questionnaires to assess the
delays in diagnosis. Provider delays were found to be significant (the
unregistered doctors or quacks being a significant cause of delays).The average
time lapse before diagnosis for rural patients was higher (67.5 days) compared to
urban patients (53.7 days). The literacy levels of the patients also had a
significant impact on the delays at diagnosis. The delay in illiterates was 60.6
days compared to 49.5 days for literates. CONCLUSIONS: The most common factor
responsible for delays in reporting and diagnosis was observed to be at the end
of the health providers, although illiteracy and lack of adequate healthcare
services also contributed significantly. Unregistered medical practitioners or
quacks contributed significantly to the delays in reporting and diagnosis of the
disease.
PMID- 22046496
TI - History of Medicine student selected components at UK medical schools: a
questionnaire-based study.
AB - OBJECTIVES: To determine the current status of History of Medicine student
selected components (SSC) at UK medical schools. This includes the frequency,
methods of delivery, assessment, and evaluation of such courses. DESIGN: An 18
item questionnaire was created, piloted, and then sent electronically in January
2010 to participants pertaining to their History of Medicine SSC provision as of
1 January 2010. Initial non-responders were re-sent the questionnaire in February
2010. SETTING: All UK medical schools. PARTICIPANTS: The History of Medicine SSC
lead or overall SSC lead at each UK medical school were contacted to ascertain
their History of Medicine SSC provision. MAIN OUTCOME MEASURES: Percentages of
History of Medicine SSCs for each objective characteristic were obtained as well
as general descriptive data. RESULTS: Fifteen of the 32 medical schools in the UK
offer a History of Medicine SSC. Eleven medical schools (offering a total of 12
SSCs) completed the questionnaire (response rate 73.3%). Eight different teaching
methods are used within the SSCs. Medical professionals most frequently deliver
the teaching, which most frequently covers the 20th and 21st centuries. Four
assessment methods are used among the SSCs, the most common being a group
presentation. Questionnaires are the most frequent method of evaluation. There
are several factors limiting the provision of some current SSCs, most commonly a
lack of staff, teaching facilities, and available time within the curriculum.
CONCLUSION: History of Medicine is being delivered more frequently in UK medical
schools than when previously researched 40 years ago. However, the subject is
still offered in a minority of the medical schools. This study offers useful
information to consider for the development of current and potential new History
of Medicine SSCs.
PMID- 22046497
TI - Effective smoking cessation interventions for COPD patients: a review of the
evidence.
AB - OBJECTIVES: To review the effectiveness of smoking cessation interventions
offered to chronic obstructive pulmonary disease (COPD) patients, and identify
barriers to quitting experienced by them, so that a more effective service can be
developed for this group. DESIGN: A rapid systematic literature review comprising
computerized searches of electronic databases, hand searches and snowballing were
used to identify both published and grey literature. SETTING: A review of studies
undertaken in north-western Europe (defined as: United Kingdom, Ireland, France,
Germany, Benelux and Nordic countries). PARTICIPANTS: COPD patients participating
in studies looking at the effectiveness of smoking cessation interventions in
this patient group, or exploring the barriers to quitting experienced by these
patients. METHOD: Quantitative and qualitative papers were selected according to
pre-specified inclusion and exclusion criteria, critically appraised, and
quantitative papers scored against the NICE Levels of Evidence standardized
hierarchy. MAIN OUTCOME MEASURE: Percentages of successful quitters and length of
quit, assessed by self-report or biochemical analysis. Among qualitative studies,
identified barriers to smoking cessation had to be explored. RESULTS: Three
qualitative and 13 quantitative papers were finally selected. Effective
interventions and barriers to smoking cessation were identified. Pharmacological
support with Buproprion combined with counselling was significantly more
efficacious in achieving prolonged abstinence than a placebo by 18.9% (95% CI 3.6
26.4%). Annual spirometry with a brief smoking cessation intervention, followed
by a personal letter from a doctor, had a significantly higher >=1 year
abstinence rate at three years among COPD patient smokers, compared to smokers
with normal lung function (P < 0.001; z = 3.93). Identified barriers to cessation
included: patient misinformation, levels of motivation, health beliefs, and poor
communication with health professionals. CONCLUSION: Despite the public health
significance of COPD, there is a lack of high-quality evidence showing which
smoking cessation support methods work for these patients. This review describes
three effective interventions, as well as predictors of quitting success that
service providers could use to improve quit rates in this group. Areas that would
benefit from urgent further research are also identified.
PMID- 22046498
TI - Presenting a practical model for governmental political mapping on road traffic
injuries in Iran in 2008: a qualitative study.
AB - OBJECTIVES: This study was conducted to assess political mapping in relation to
road traffic injuries (RTIs) management and prevention to present a practical
model for RTIs. DESIGN: A phenomenological qualitative study was developed to
identify stakeholders on RTI in Iran in 2008. SETTING: The designed questions
were discussed by systematic discussion with the relevant specialists. After
receiving written consent from the main responsible stakeholders, the
questionnaire was filled in by trained experts. Themes were determined and
content was analysed in each part. PARTICIPANTS: Main responsible stakeholders.
MAIN OUTCOME MEASURES: By comparing other countries' political mappings which
were found in the library and by Internet searching, political mapping of RTI in
Iran was suggested. RESULTS: Subjects were 26 experts from governmental and non
governmental organizations. The main proposed leading agencies were traffic
police and presidency (13% each). Findings showed that only 31% of our political
mapping was formed according to the World Health Organization (WHO). In 94% of
cases, the involved organizations had unspecified roles; the reason was poor
monitoring for RTI in 39% of organizations. Lack of adequate authority and
suitable legislation, appropriate laws and tasks definition were 94% and 18%,
respectively. The most essential policy to overcome problems was defined as
appropriate legislation (21%), and the most frequent type of support needed was
mentioned as adequate budgeting (25%). CONCLUSION: Traffic police can play the
leading agency role by government support, with strong leadership, appropriate
legislation, defined tasks and adequate budget.
PMID- 22046499
TI - Disseminated mucocutaneous herpes simplex in an atopic individual.
PMID- 22046500
TI - Primary care strategies to improve childhood immunisation uptake in developed
countries: systematic review.
AB - OBJECTIVES: To conduct a systematic review of strategies to optimize immunisation
uptake within preschool children in developed countries. DESIGN: Systematic
review. SETTING: Developed countries PARTICIPANTS: Preschool children who were
due, or overdue, one or more of their routine primary immunisations. MAIN OUTCOME
MEASURES: Increase in the proportion of the target population up to date with
standard recommended universal vaccinations. RESULTS: Forty-six studies were
included for analysis, published between 1980 and 2009. Twenty-six studies were
randomized controlled trials, 11 were before and after trials, and nine were
controlled intervention trials. Parental reminders showed a statistically
significant increase in immunisation rates in 34% of included intervention arms.
These effects were reported with both generic and specific reminders and with all
methods of reminders and recall. Strategies aimed at immunisation providers were
also shown to improve immunisation rates with a median change in immunisation
rates of 7% when reminders were used, 8% when educational programmes were used
and 19% when feedback programmes were used. CONCLUSION: General practitioners are
uniquely positioned to influence parental decisions on childhood immunisation. A
variety of strategies studied in primary care settings have been shown to improve
immunisation rates, including parental and healthcare provider reminders.
PMID- 22046501
TI - The potential role of oestrogens in relapse of recurrent affective psychosis.
PMID- 22046503
TI - Pharmacogenetics and age-related macular degeneration.
AB - Pharmacogenetics seeks to explain interpatient variability in response to
medications by investigating genotype-phenotype correlations. There is a small
but growing body of data regarding the pharmacogenetics of both nonexudative and
exudative age-related macular degeneration. Most reported data concern
polymorphisms in the complement factor H and age-related maculopathy
susceptibility 2 genes. At this time, the data are not consistent and no definite
conclusions may be drawn. As clinical trials data continue to accumulate, these
relationships may become more apparent.
PMID- 22046502
TI - Current status of immunomodulatory and cellular therapies in preclinical and
clinical islet transplantation.
AB - Clinical islet transplantation is a beta-cell replacement strategy that
represents a possible definitive intervention for patients with type 1 diabetes,
offering substantial benefits in terms of lowering daily insulin requirements and
reducing incidences of debilitating hypoglycemic episodes and unawareness.
Despite impressive advances in this field, a limiting supply of islets,
inadequate means for preventing islet rejection, and the deleterious diabetogenic
and nephrotoxic side effects associated with chronic immunosuppressive therapy
preclude its wide-spread applicability. Islet transplantation however allows a
window of opportunity for attempting various therapeutic manipulations of islets
prior to transplantation aimed at achieving superior transplant outcomes. In this
paper, we will focus on the current status of various immunosuppressive and
cellular therapies that promote graft function and survival in preclinical and
clinical islet transplantation with special emphasis on the tolerance-inducing
capacity of regulatory T cells as well as the beta-cells regenerative capacity of
stem cells.
PMID- 22046504
TI - New and old mechanisms associated with hypertension in the elderly.
AB - Hypertension is a widely prevalent and important risk factor for cardiovascular
diseases that increase with aging. The hallmark of hypertension in the elderly is
increased vascular dysfunction. However, the molecular mechanisms by which
increased blood pressure leads to vascular injury and impaired endothelial
function are not well defined. In the present paper, we will analyze several
mechanisms described in the scientific literature involved in hypertension in the
elderly as endothelial dysfunction, increased oxygen delivery to tissues,
inflammation, cellular apoptosis, and increased concentration of active
metabolites. Also, we will focus on new molecular mechanisms involved in
hypertension such as telomeres shortening, progenitor cells, circulating
microparticles, and epigenetic factors that have appeared as possible causes of
hypertension in the elderly. These molecular mechanisms may elucidate different
origin for hypertension in the elderly and provide us with new targets for
hypertension treatment.
PMID- 22046505
TI - An Examination of Palliative or End-of-Life Care Education in Introductory
Nursing Programs across Canada.
AB - An investigation was done to assess for and describe the end-of-life education
provided in Canadian nursing programs to prepare students for practice. All 35
university nursing schools/faculties were surveyed in 2004; 29 (82.9%) responded.
At that time, all but one routinely provided this education, with that school
developing a course (implemented the next year). As compared to past surveys,
this survey revealed more class time, practicum hours, and topics covered, with
this content and experiences deliberately planned and placed in curriculums. A
check in 2010 revealed that all of these schools were providing death education
similar to that described in 2004. These findings indicate that nurse educators
recognize the need for all nurses to be prepared to care for dying persons and
their families. Regardless, more needs to be done to ensure novice nurses feel
capable of providing end-of-life care. Death education developments will be
needed as deaths increase with population aging.
PMID- 22046506
TI - MAP Kinases and Prostate Cancer.
AB - The three major mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK are
signal transducers involved in a broad range of cell functions including
survival, apoptosis, and cell differentiation. Whereas JNK and p38 have been
generally linked to cell death and tumor suppression, ERK plays a prominent role
in cell survival and tumor promotion, in response to a broad range of stimuli
such as cytokines, growth factors, ultraviolet radiation, hypoxia, or
pharmacological compounds. However, there is a growing body of evidence
supporting that JNK and p38 also contribute to the development of a number of
malignances. In this paper we focus on the involvement of the MAPK pathways in
prostate cancer, including the less-known ERK5 pathway, as pro- or antitumor
mediators, through their effects on apoptosis, survival, metastatic potential,
and androgen-independent growth.
PMID- 22046507
TI - Neurospora crassa Light Signal Transduction Is Affected by ROS.
AB - In the ascomycete fungus Neurospora crassa blue-violet light controls the
expression of genes responsible for differentiation of reproductive structures,
synthesis of secondary metabolites, and the circadian oscillator activity. A
major photoreceptor in Neurospora cells is WCC, a heterodimeric complex formed by
the PAS-domain-containing polypeptides WC-1 and WC-2, the products of genes white
collar-1 and white collar-2. The photosignal transduction is started by
photochemical activity of an excited FAD molecule noncovalently bound by the LOV
domain (a specialized variant of the PAS domain). The presence of zinc fingers
(the GATA-recognizing sequences) in both WC-1 and WC-2 proteins suggests that
they might function as transcription factors. However, a critical analysis of the
phototransduction mechanism considers the existence of residual light responses
upon absence of WCC or its homologs in fungi. The data presented point at
endogenous ROS generated by a photon stimulus as an alternative input to pass on
light signals to downstream targets.
PMID- 22046508
TI - Macrophage migration inhibitory factor: a multifunctional cytokine in rheumatic
diseases.
AB - Macrophage migration inhibitory factor (MIF) was originally identified in the
culture medium of activated T lymphocytes as a soluble factor that inhibited the
random migration of macrophages. MIF is now recognized to be a multipotent
cytokine involved in the regulation of immune and inflammatory responses.
Moreover, the pivotal nature of its involvement highlights the importance of MIF
to the pathogenesis of various inflammatory disorders and suggests that blocking
MIF may be a useful therapeutic strategy for treating these diseases. This paper
discusses the function and expressional regulation of MIF in several rheumatic
diseases and related conditions.
PMID- 22046509
TI - Item Response Theory Analysis of Two Questionnaire Measures of Arthritis-Related
Self-Efficacy Beliefs from Community-Based US Samples.
AB - Using item response theory (IRT), we examined the Rheumatoid Arthritis Self
efficacy scale (RASE) collected from a People with Arthritis Can Exercise RCT
(346 participants) and 2 subscales of the Arthritis Self-efficacy scale (ASE)
collected from an Active Living Every Day (ALED) RCT (354 participants) to
determine which one better identifies low arthritis self-efficacy in community
based adults with arthritis. The item parameters were estimated in Multilog using
the graded response model. The 2 ASE subscales are adequately explained by one
factor. There was evidence for 2 locally dependent item pairs; two items from
these pairs were removed when we reran the model. The exploratory factor analysis
results for RASE showed a multifactor solution which led to a 9-factor solution.
In order to perform IRT analysis, one item from each of the 9 subfactors was
selected. Both scales were effective at measuring a range of arthritis SE.
PMID- 22046510
TI - Cutaneous polyarteritis nodosa in childhood: a case report and review of the
literature.
AB - Polyarteritis nodosa is a rare vasculitis of childhood. Cutaneous PAN (cPAN) is
limited to the skin, muscles, joints, and peripheral nerves. We describe a 7.5
year-old girl with cPAN presenting initially as massive cervical edema who later
went on to develop subcutaneous nodules, livedo reticularis, myositis, arthritis,
and mononeuritis multiplex. The use of corticosteroids resulted in initial
clinical improvement, but symptom recurrence necessitated disease modifying
antirheumatic drugs and biologic therapy. We review a further 119 reports of
biopsy proven cPAN in the literature. A majority of patients (96.6%) had
cutaneous involvement; musculoskeletal involvement was common and included both
articular (58.0%) and muscular (42.9%) symptoms, and nervous system involvement
was least common (18.5%). Corticosteroids were used in the majority of patients
(85.7%), followed by use of disease modifying antirheumatic drugs (33.0%),
nonsteroidal anti-inflammatory drugs (10.7%), and intravenous immunoglobulin
(9.8%). Therapy of cPAN with biologics has only been reported in 2 patients, and
we report the first patient treated with Rituximab. A diagnosis of cPAN should be
considered in a child with fever, vasculitic rash, and musculoskeletal symptoms.
Most children respond to corticosteroids and have a benign course, but some
require disease modifying antirheumatic drugs and biologic therapies.
PMID- 22046511
TI - Staphylococcus aureus Decolonization Protocol Decreases Surgical Site Infections
for Total Joint Replacement.
AB - We investigated the effects of implementation of an institution-wide screening
and decolonization protocol on the rates of deep surgical site infections (SSIs)
in patients undergoing primary knee and hip arthroplasties. 2058 patients were
enrolled in this study: 1644 patients in the treatment group and 414 in the
control group. The treatment group attended preoperative admission testing (PAT)
clinic where they were screened for MSSA and MRSA colonization. All patients were
provided a 5-day course of nasal mupirocin and a single preoperative
chlorhexidine shower. Additionally, patients colonized with MRSA received
Vancomycin perioperative prophylaxis. The control group did not attend PAT nor
receive mupirocin treatment and received either Ancef or Clindamycin for
perioperative antibiotic prophylaxis. There were a total of 6 deep infections in
the control group (1.45%) and 21 in the treatment group (1.28%); this represented
a decrease of 13% (P = .809) in the treatment versus control group. This decrease
represented a positive trend in favor of staphylococcus screening, decolonization
with mupirocin, and perioperative Vancomycin for known MRSA carriers.
PMID- 22046512
TI - Efficacy and effectiveness of exercise on tender points in adults with
fibromyalgia: a meta-analysis of randomized controlled trials.
AB - Fibromyalgia is a major public health problem affecting an estimated 200 to 400
million people worldwide. The purpose of this study was to use the meta-analytic
approach to determine the efficacy and effectiveness of randomized controlled
exercise intervention trials (aerobic, strength training, or both) on tender
points (TPs) in adults with fibromyalgia. Using random effects models and 95%
confidence intervals (CI), a statistically significant reduction in TPs was
observed based on per-protocol analyses (8 studies representing 322 participants)
but not intention-to-treat analyses (5 studies representing 338 participants)
(per-protocol, g, -0.68, 95% CI, -1.16, -0.20; intention-to-treat, g, -0.24, 95%
CI, -0.62, 0.15). Changes were equivalent to relative reductions of 10.9% and
6.9%, respectively, for per-protocol and intention-to-treat analyses. It was
concluded that exercise is efficacious for reducing TPs in women with FM.
However, a need exists for additional well-designed and reported studies on this
topic.
PMID- 22046513
TI - Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and
progression of disease.
AB - Obesity has been considered a risk factor for osteoarthritis and it is usually
accepted that obesity contributes to the development and progression of
osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent
advances in the physiology of white adipose tissue evidenced that fat cells
produce a plethora of factors, called adipokines, which have a critical role in
the development of ostearthritis, besides to mechanical effects. In this paper,
we review the role of adipokines and highlight the cellular and molecular
mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize
how defining the role of adipokines has broadned our understanding of the
diversity of factors involved in the genesis and progression of osteoarthritis in
the hope of modifying it to prevent and treat diseases.
PMID- 22046514
TI - An Eccentrically Biased Rehabilitation Program Early after TKA Surgery.
AB - Rehabilitation services are less-studied aspects of the management following
total knee arthroplasty (TKA) despite long-term suboptimal physical functioning
and chronic deficits in muscle function. This paper describes the preliminary
findings of a six-week (12 session) eccentrically-biased rehabilitation program
targeted at deficits in physical function and muscle function, initiated one
month following surgery. A quasiexperimental, one group, pretest-posttest study
with thirteen individuals (6 female, 7 male; mean age 57 +/- 7 years) examined
the effectiveness of an eccentrically-biased rehabilitation program. The program
resulted in improvements in the primary physical function endpoints (SF-36
physical component summary and the six-minute walk test) with increases of 59%
and 47%, respectively. Muscle function endpoints (knee extension strength and
power) also increased 107% and 93%, respectively. Eccentrically-biased exercise
used as an addition to rehabilitation may help amplify and accelerate physical
function following TKA surgery.
PMID- 22046515
TI - Coxarthritis as the presenting symptom of Gaucher disease type 1.
AB - Gaucher disease (GD) type 1 is the most common lysosomal storage disorder due to
beta glucocerebrosidase deficiency leading to an abnormal accumulation of its
substrate, glucocerebroside, in the mononuclear phagocyte system. The disease
presentation is usually characterized by signs and symptoms related to
hypersplenism, such as splenomegaly, anaemia, thrombocytopenia and leucopenia.
Skeletal disease may occur later for the infiltration of bone marrow by
macrophages infiltration and bone resorption: bone involvement may be
heterogeneously manifested by symptoms ranging from bone crisis to avascular
necrosis, osteoporosis and defect in remodeling of long bones. Herein, we report
a patient in whom the osteoarticular involvement has been the only symptom of the
disease stressing that this unusual presentation of GD has prompted a wide
differential diagnosis with more common forms of coxitis.
PMID- 22046516
TI - Complementary and alternative exercises for management of osteoarthritis.
AB - Osteoarthritis (OA) is a chronic condition characterized by degeneration of
cartilage and its underlying bone within a joint. With no cure currently
available, the goals of treating OA are to alleviate pain, maintain, or improve
joint mobility, increase the muscle strength of the joints, and minimize the
disabling effects of the disease. Recent research has suggested that
complementary and alternative medicine (CAM) exercises may improve OA symptoms.
This paper covers CAM mind-body exercises-Tai Chi, qigong, and yoga-for OA
management and evaluates their benefits in pain reduction, muscle strength,
physical function, stiffness, balance, fear of falling, self-efficacy, quality of
life, and psychological outcomes in patients with OA, based on randomized
controlled trials published. Findings from the literature suggest that CAM
exercises demonstrate considerable promise in the management of OA. Future
studies require rigorous randomized controlled trials with larger sample sizes.
PMID- 22046517
TI - Current surgical treatment of knee osteoarthritis.
AB - Osteoathritis (OA) of the knee is common, and the chances of suffering from OA
increase with age. Its treatment should be initially nonoperative-and requires
both pharmacological and nonpharmacological treatment modalities. If conservative
therapy fails, surgery should be considered. Surgical treatments for knee OA
include arthroscopy, cartilage repair, osteotomy, and knee arthroplasty.
Determining which of these procedures is most appropriate depends on several
factors, including the location, stage of OA, comorbidities on the one side and
patients suffering on the other side. Arthroscopic lavage and debridement is
often carried out, but does not alter disease progression. If OA is limited to
one compartment, unicompartmental knee arthroplasty or unloading osteotomy can be
considered. They are recommended in young and active patients in regard to the
risks and limited durability of total knee replacement. Total arthroplasty of the
knee is a common and safe method in the elderly patients with advanced knee OA.
This paper summarizes current surgical treatment strategies for knee OA, with a
focus on the latest developments, indications and level of evidence.
PMID- 22046519
TI - The Influence of Radiographic Severity on the Relationship between Muscle
Strength and Joint Loading in Obese Knee Osteoarthritis Patients.
AB - Objective. To investigate the relationship between knee muscle strength and the
external knee adduction moment during walking in obese knee osteoarthritis
patients and whether disease severity influences this relationship. Methods. This
cross-sectional study included 136 elderly obese (BMI > 30) adults with
predominant medial knee osteoarthritis. Muscle strength, standing radiographic
severity as measured by the Kellgren and Lawrence scale, and the peak external
knee adduction moment were measured at self-selected walking speed. Results.
According to radiographic severity, patients were classified as "less severe" (KL
1-2, N = 73) or "severe" (KL 3-4, N = 63). A significant positive association was
demonstrated between the peak knee adduction moment and hamstring muscle strength
in the whole cohort (P = .047). However, disease severity did not influence the
relationship between muscle strength and dynamic medial knee joint loading.
Severe patients had higher peak knee adduction moment and more varus malalignment
(P < .001). Conclusion. Higher hamstring muscle strength relates to higher
estimates of dynamic knee joint loading in the medial compartment. No such
relationship existed for quadriceps muscle strength. Although cross sectional,
the results suggest that hamstrings function should receive increased attention
in future studies and treatments that aim at halting disease progression.
PMID- 22046518
TI - Quantitative cartilage imaging in knee osteoarthritis.
AB - Quantitative measures of cartilage morphology (i.e., thickness) represent
potentially powerful surrogate endpoints in osteoarthritis (OA). These can be
used to identify risk factors of structural disease progression and can
facilitate the clinical efficacy testing of structure modifying drugs in OA. This
paper focuses on quantitative imaging of articular cartilage morphology in the
knee, and will specifically deal with different cartilage morphology outcome
variables and regions of interest, the relative performance and relationship
between cartilage morphology measures, reference values for MRI-based knee
cartilage morphometry, imaging protocols for measurement of cartilage morphology
(including those used in the Osteoarthritis Initiative), sensitivity to change
observed in knee OA, spatial patterns of cartilage loss as derived by subregional
analysis, comparison of MRI changes with radiographic changes, risk factors of
MRI-based cartilage loss in knee OA, the correlation of MRI-based cartilage loss
with clinical outcomes, treatment response in knee OA, and future directions of
the field.
PMID- 22046520
TI - Serum leptin concentration positively correlates with body weight and total fat
mass in postmenopausal Japanese women with osteoarthritis of the knee.
AB - The objective of the present study was to identify factors correlated with the
serum leptin concentration in women with knee OA. Fifty postmenopausal Japanese
women with knee OA (age: 50-88 years) were recruited in our outpatient clinic.
Plain radiographs of the knee were taken, and urine and blood samples were
collected. Dual-energy X-ray absorptiometry (DXA) scanning was performed for the
whole body and lumbar spine, and factors correlated with the serum leptin
concentration were identified. A simple linear regression analysis showed that
body weight, body mass index, whole-body bone mineral density (BMD), total fat
mass, and total fat percentage, but not age, height, lumbar spine BMD, lean body
mass, serum and urinary bone turnover markers, or the radiographic grade of knee
OA, were significantly correlated with the serum leptin concentration. A multiple
regression analysis showed that among these factors, only body weight and total
fat mass exhibited a significant positive correlation with the serum leptin
concentration. These results suggest that the serum leptin concentration might be
related to increases in body weight and total fat mass, but not to BMD or bone
turnover markers, in postmenopausal women with OA.
PMID- 22046521
TI - The self-administered patient satisfaction scale for primary hip and knee
arthroplasty.
AB - Introduction. The objective of this study was to develop a short self-report
questionnaire for evaluating patient satisfaction with the outcome of hip and
knee replacement surgery. Methods. This scale consists of four items focusing on
satisfaction with the extent of pain relief, improvement in ability to perform
home or yard work, ability to perform recreational activities, and overall
satisfaction with joint replacement. This instrument does not measure
satisfaction with process of care. The responses are scored on a Likert scale,
with the total score ranging from 25 to 100 per question. The instrument was
tested on 1700 patients undergoing primary total hip and total knee replacement
surgery, evaluated preoperatively, at 12 weeks, and one year postoperatively.
Psychometric testing included internal consistency, measured with Cronbach's
alpha, and convergent validity, measured by correlation with changes in measures
of health status between the preoperative, 12-week, and one-year evaluations.
Results. The internal consistency (reliability) of the scale, measured by the
Cronbach's alpha, ranged from 0.86 to 0.92. The scale demonstrated substantial
ceiling effects at 1 year. The scale scores correlated modestly with the absolute
SF-36 PCS and WOMAC scores (rho = 0.56-0.63 and also with the WOMAC change scores
(rho = 0.38-0.46) at both 12-week and 1-year followups. Conclusions. This
instrument is valid and reliable for measuring patient satisfaction following
primary hip and knee arthroplasty and could be further evaluated for use with
other musculoskeletal interventions.
PMID- 22046523
TI - Rheumatoid factor and its interference with cytokine measurements: problems and
solutions.
AB - Use of cytokines as biomarkers for disease is getting more widespread. Cytokines
are conveniently determined by immunoassay, but interference from present
antibodies is known to cause problems. In rheumatoid arthritis (RA), interference
of rheumatoid factor (RF) may be problematic. RF covers a group of autoantibodies
from immunoglobulin subclasses and is present in 65-80% of RA patients. Partly
removal of RF is possible by precipitation. This study aims at determining the
effects of presence of RF in blood and synovial fluid on cytokine measurements in
samples from RA patients and finding possible solutions for recognized problems.
IL-1beta, IL-4, IL-6, and IL-8 were determined with multiplex immunoassays (MIA)
in samples from RA patients prior to and after polyethylene glycol (PEG 6000)
precipitation. Presence of RF does interfere with MIA. PEG 6000 precipitation
abolishes this RF interference. We recommend PEG precipitation for all
immunoassay measurements of plasma samples from RA patients.
PMID- 22046522
TI - Developmental mechanisms in articular cartilage degradation in osteoarthritis.
AB - Osteoarthritis is the most common arthritic condition, which involves progressive
degeneration of articular cartilage. The most recent accomplishments have
significantly advanced our understanding on the mechanisms of the disease
development and progression. The most intriguing is the growing evidence
indicating that extracellular matrix destruction in osteoarthritic articular
cartilage resembles that in the hypertrophic zone of fetal growth plate during
endochondral ossification. This suggests common regulatory mechanisms of matrix
degradation in OA and in the development and can provide new approaches for the
treatment of the disease by targeting reparation of chondrocyte phenotype.
PMID- 22046524
TI - Popliteal cysts in paediatric patients: clinical characteristics and imaging
features on ultrasound and MRI.
AB - Popliteal cysts, or Baker cysts, are considered rare in children and may exhibit
particular features, as compared with adults. We studied data from 80 paediatric
patients with 55 Baker cysts, examined over a period of 7 years, and correlated
clinical presentation with findings on ultrasonography and MRI. Prevalence of
popliteal cysts was 57% in arthritic knees, 58% with hypermobility syndrome, and
28% without risk factors. Only one patient had a trauma history and showed an
ipsilateral cyst. Mean cyst volume was 3.4 mL; cysts were larger in boys.
Patients with arthritis had echogenic cysts in 53%. Cyst communication with the
joint space was seen in 64% on ultrasonography and 86% on MRI. In conclusion,
Baker cysts are a common finding in a clinically preselected paediatric
population. Children with Baker cysts should be assessed for underlying arthritis
and inherited joint hypermobility, while sporadic Baker cysts appear to be
common, as well.
PMID- 22046525
TI - The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis.
AB - Several clinical studies have demonstrated that the humanized anti-interleukin-6
(IL-6) receptor antibody tocilizumab (TCZ) improves clinical symptoms and
prevents progression of joint destruction in rheumatoid arthritis (RA). However,
the precise mechanism by which IL-6 blockade leads to the improvement of RA is
not well understood. IL-6 promotes synovitis by inducing neovascularization,
infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone
resorption by inducing osteoclast formation via the induction of RANKL in
synovial cells, and cartilage degeneration by producing matrix metalloproteinases
(MMPs) in synovial cells and chondrocytes. Moreover, IL-6 is involved in
autoimmunity by altering the balance between T(h)17 cells and T(reg). IL-6 also
acts on changing lipid concentrations in blood and on inducing the production of
hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major
player in the pathogenesis of RA, and current evidence indicates that the
blockade of IL-6 is a beneficial therapy for RA patients.
PMID- 22046526
TI - Patella Eversion Reduces Early Knee Range of Motion and Muscle Torque Recovery
after Total Knee Arthroplasty: Comparison between Minimally Invasive Total Knee
Arthroplasty and Conventional Total Knee Arthroplasty.
AB - We hypothesized that patella eversion during total knee arthroplasty (TKA)
reduces early return of active knee extension and flexion, quadriceps muscle
strength, and postoperative pain. In 100 conventional TKA knees and 100 minimally
invasive TKA (MIS TKA) knees, we compared knee range of motion (ROM),
postoperative pain, and quadriceps muscle strength at 1 day, 4 days, 1 week, 2
weeks, 3 weeks, 4 weeks, 12 weeks, 1 year, and 5 years after surgery. The
differences of surgical approach between MIS TKA and conventional TKA of this
study are length of skin incision with subcutaneal flap and patella eversion. In
MIS TKA, skin incision is shorter than conventional TKA. Furthermore, patella is
not everted in MIS TKA procedure. There were no significant differences in
preoperative factors. Postoperative improvement of ROM, postoperative muscle
strength recovery, and postoperative improvement of visual analog scale were
faster in patients with MIS TKA when compared to that in patients with
conventional TKA. On the other hand, no significant difference was observed in
complication, 5-year clinical results of subjective knee function score, and the
postoperative component angle and lower leg alignment. These results indicate
that patella eversion may affect muscle strength recovery and postoperative pain.
PMID- 22046528
TI - Correlation between Oxidative Stress and Thyroid Function in Patients with
Nephrotic Syndrome.
AB - Background. The present study is to look for a correlation between oxidative
stress and thyroid function in patients with the nephrotic syndrome in the
remission phase as well as in a persistent proteinuric state. Introduction.
Nephrotic syndrome is a form of chronic kidney disease due to which blood loses
protein through the urine. We wanted to know if there was an increased loss of
thyroid hormones in urine affecting thyroid function. Methods. 60 patients with
nephrotic syndrome and 20 healthy non-proteinuric individuals as control subjects
were enrolled in the study. We measured their serum tri-iodothyronine, thyroxine
and thyroid-stimulating hormone. Estimation of lipid peroxidation (LPx) catalase,
superoxide dismutase (SOD), and Glutathione peroxidase (GPx) were carried out by
standard methods. Results. TSH was elevated in the nephrotic patients compared to
controls, while TT4 and TT3 were significantly lower in the patients than in
controls. Lipid Peroxidation and GPx were significantly higher in the nephrotic
syndrome patients than in the controls, while SOD and catalase were significantly
lower than in patients than in the control subjects. Conclusion. Nephrotic
patients can lose significant amounts of thyroid hormones along with protein in
urine, which can affect thyroid status, but this is reversible on remission.
PMID- 22046529
TI - Cancer, senescence, and aging: translation from basic research to clinics.
PMID- 22046531
TI - Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age
Categories.
AB - Background. Strategies combining pretest clinical assessment and D-dimers
measurement efficiently and safely rule out venous thromboembolism events (VTE)
in low- and intermediate-risk patients. Objectives. As process of ageing is
associated with altered concentrations of coagulation markers including an
increase in D-dimers levels, we investigated whether D-dimers could reliably rule
out VTE across age categories. Method. We prospectively assessed the test
performance in 1,004 patients visiting the emergency department during the 6
month period with low or intermediate risk of VTE who also received additional
diagnostic procedures. Results. 67 patients had VTE with D-dimers levels above
the threshold, and 3 patients displayed D-dimers levels below the threshold. We
observed that specificity of D-dimers test decreased in an age-dependent manner.
However, sensitivity and negative predictive value remained at very high level in
each age category including older patients. Conclusion. We conclude that, even
though D-dimers level could provide numerous false positive results in elderly
patients, its high sensitivity could reliably help physicians to exclude the
diagnosis of VTE in every low- and intermediate-risk patient.
PMID- 22046530
TI - Shorter leukocyte telomere length in midlife women with poor sleep quality.
AB - Background. Accumulating evidence supports leukocyte telomere length (LTL) as a
biological marker of cellular aging. Poor sleep is a risk factor for age-related
disease; however, the extent to which sleep accounts for variation in LTL is
unknown. Methods. The present study examined associations of self-reported sleep
duration, onset latency, and subjective quality with LTL in a community-dwelling
sample of 245 healthy women in midlife (aged 49-66 years). Results. While sleep
duration and onset latency were unrelated to LTL, women reporting poorer sleep
quality displayed shorter LTL (r = 0.14, P = 0.03), independent of age, BMI,
race, and income (b = 55.48, SE = 27.43, P = 0.04). When analyses were restricted
to participants for whom sleep patterns were chronic, poorer sleep quality
predicted shorter LTL independent of covariates and perceived psychological
stress. Conclusions. This study provides the first evidence that poor sleep
quality explains significant variation in LTL, a marker of cellular aging.
PMID- 22046527
TI - Biomechanical influence of cartilage homeostasis in health and disease.
AB - There is an urgent demand for long term solutions to improve osteoarthritis
treatments in the ageing population. There are drugs that control the pain but
none that stop the progression of the disease in a safe and efficient way.
Increased intervention efforts, augmented by early diagnosis and integrated
biophysical therapies are therefore needed. Unfortunately, progress has been
hampered due to the wide variety of experimental models which examine the effect
of mechanical stimuli and inflammatory mediators on signal transduction pathways.
Our understanding of the early mechanopathophysiology is poor, particularly the
way in which mechanical stimuli influences cell function and regulates matrix
synthesis. This makes it difficult to identify reliable targets and design new
therapies. In addition, the effect of mechanical loading on matrix turnover is
dependent on the nature of the mechanical stimulus. Accumulating evidence
suggests that moderate mechanical loading helps to maintain cartilage integrity
with a low turnover of matrix constituents. In contrast, nonphysiological
mechanical signals are associated with increased cartilage damage and
degenerative changes. This review will discuss the pathways regulated by
compressive loading regimes and inflammatory signals in animal and in vitro 3D
models. Identification of the chondroprotective pathways will reveal novel
targets for osteoarthritis treatments.
PMID- 22046532
TI - Ambulance Crash Characteristics in the US Defined by the Popular Press: A
Retrospective Analysis.
AB - Ambulance crashes are a significant risk to prehospital care providers, the
patients they are carrying, persons in other vehicles, and pedestrians. No
uniform national transportation or medical database captures all ambulance
crashes in the United States. A website captures many significant ambulance
crashes by collecting reports in the popular media (the website is mentioned in
the introduction). This report summaries findings from ambulance crashes for the
time period of May 1, 2007 to April 30, 2009. Of the 466 crashes examined, 358
resulted in injuries to prehospital personnel, other vehicle occupants, patients
being transported in the ambulance, or pedestrians. A total of 982 persons were
injured as a result of ambulance crashes during the time period. Prehospital
personnel were the most likely to be injured. Provider safety can and should be
improved by ambulance vehicle redesign and the development of improved occupant
safety restraints. Seventy-nine (79) crashes resulted in fatalities to some
member of the same groups listed above. A total of 99 persons were killed in
ambulance crashes during the time period. Persons in other vehicles involved in
collisions with ambulances were the most likely to die as a result of crashes. In
the urban environment, intersections are a particularly dangerous place for
ambulances.
PMID- 22046533
TI - Difficult Airway Management Algorithm in Emergency Medicine: Do Not Struggle
against the Patient, Just Skip to Next Step.
AB - We report a case of prehospital "cannot intubate" and "cannot ventilate"
scenarios successfully managed by strictly following a difficult airway
management algorithm. Five airway devices were used: the Macintosh laryngoscope,
the gum elastic Eschmann bougie, the LMA Fastrach, the Melker cricothyrotomy
cannula, and the flexible fiberscope. Although several airway devices were used,
overall airway management duration was relatively short, at 20 min, because for
each scenario, failed primary and secondary backup devices were quickly abandoned
after 2 failed attempts, each attempt of no more than 2 min in duration, in favor
of the tertiary rescue device. Equally, all three of these rescue devices failed,
an uncuffed cricothyroidotomy cannula was inserted to restore optimal arterial
oxygenation until a definitive airway was secured in the ICU using a flexible
fiberscope. Our case reinforces the need to strictly follow a difficult airway
management algorithm that employs a limited number of effective devices and
techniques, and highlights the imperative for early activation of successive
preplanned steps of the algorithm.
PMID- 22046534
TI - Wenckebach Block due to Hyperkalemia: A Case Report.
AB - Hyperkalemia is a commonly encountered electrolyte abnormality that can
significantly alter normal cardiac conduction. Potentially lethal dysrhythmias
associated with hyperkalemia include complete heart block and Mobitz Type II
second-degree AV block. We report a unique case of Mobitz Type 1 second-degree
atrioventricular (AV) block, known commonly as Wenckebach, due to hyperkalemia.
The patient's symptoms and electrocardiogram (ECG) evidence of Wenckebach block
resolved with lowering of serum potassium levels, with subsequent ECG showing
first-degree AV block. This paper highlights an infrequently reported dysrhythmia
associated with hyperkalemia that emergency physicians should be familiar with.
PMID- 22046535
TI - A Patient with Splenic Artery Aneurysm Rupture and the Importance of Rapid
Sonography in the ED.
AB - We report a case of a splenic artery aneurysm rupture presenting with shock which
required timely embolization therapy. This case demonstrates how the rapid use of
bedside ultrasound by emergency department (ED) physicians can help identify the
cause of shock and, therefore, initiate appropriate treatment quickly even if the
cause is rare, as in this case.
PMID- 22046536
TI - The emergency management and treatment of severe burns.
AB - Burn injuries continue to cause morbidity and mortality internationally. Despite
international collaborations and preventative measures, there are still many
cases reported in high- and low-income countries. The treatment of these patients
is often protracted and requires extensive resources. The adequate resuscitation
of these patients coupled with meticulous wound care can have a huge impact on
their outcome. The authors present a simple guideline for the initial management
of severe burns which is utilised by the South African Burn Society and is based
on the guidelines of the American Burn Association and the Australian and New
Zealand Burn Association.
PMID- 22046537
TI - Expectations of Care, Perceived Safety, and Anxiety following Acute Behavioural
Disturbance in the Emergency Department.
AB - Objective. We explored perspectives of emergency department users (patients and
visitors) regarding the management of acute behavioural disturbances in the
emergency department and whether these disturbances influenced their levels of
anxiety. Methods. Emergency department patients and visitors were surveyed using
the State-Trait Anxiety Inventory, and a purpose-designed questionnaire and
semistructured interview. The main outcome measures were themes that emerged from
the questionnaires, the interviews, and scores from the state component of the
State-Trait Anxiety Inventory. Results. 70 participants were recruited. Users of
the emergency department preferred behaviourally disturbed people be managed in a
separate area from the general emergency department population so that the
disturbance was inaudible (n = 32) and out of view (n = 40). The state anxiety
levels of those that witnessed an acute behavioural disturbance were within the
normal range and did not differ to that of ED patients that were not present
during such a disturbance (median, control = 37, Code Grey = 33). Conclusions.
Behavioural disturbances in the emergency department do not provoke anxiety in
other users. However, there is a preference that such disturbances be managed out
of visual and audible range. Innovative design features may be required to
achieve this.
PMID- 22046538
TI - Micropower impulse radar: a novel technology for rapid, real-time detection of
pneumothorax.
AB - Pneumothorax detection in emergency situations must be rapid and at the point of
care. Current standards for detection of a pneumothorax are supine chest X-rays,
ultrasound, and CT scans. Unfortunately these tools and the personnel necessary
for their facile utilization may not be readily available in acute circumstances,
particularly those which occur in the pre-hospital setting. The decision to treat
therefore, is often made without adequate information. In this report, we
describe a novel hand-held device that utilizes Micropower Impulse Radar to
reliably detect the presence of a pneumothorax. The technology employs ultra wide
band pulses over a frequency range of 500 MHz to 6 GHz and a proprietary
algorithm analyzes return echoes to determine if a pneumothorax is present with
no user interpretation required. The device has been evaluated in both trauma and
surgical environments with sensitivity of 93% and specificity of 85%. It is has
the CE Mark and is available for sale in Europe. Post market studies are planned
starting in May of 2011. Clinical studies to support the FDA submission will be
completed in the first quarter of 2012.
PMID- 22046539
TI - Improved survival with therapeutic hypothermia after cardiac arrest with cold
saline and surfacing cooling: keep it simple.
AB - Aim. To evaluate whether the introduction of a therapeutic hypothermia (TH)
protocol consisting of cold saline infusion and surface cooling would be
effective in targeting mild therapeutic hypothermia (32-34 degrees C).
Additionally, to evaluate if TH would improve survival after cardiac arrest.
Design. Before-after design. Setting. General Intensive Care Unit (ICU) at an
urban general hospital with 470 beds. Patients and Methods. Patients admitted in
the ICU after cardiac arrest between 2004 and 2009 were included. Effectiveness
of the TH protocol to achieve the targeted temperature was evaluated. Hospital
mortality was compared before (October 2004-March 2006) and after (April 2006
September 2009) the protocol implementation. Results. Hundred and thirty patients
were included, 75 patients were not submitted to TH (before TH group), and 55
were submitted to TH (TH group). There were no significant differences concerning
baseline, ICU, and cardiac arrest characteristics between both groups. There was
a significant reduction in hospital mortality from 61% (n = 46) in the before TH
group to 40% (n = 22) in the TH group. Conclusion. Our protocol consisting of
cold saline infusion and surface cooling might be effective in inducing and
maintaining mild therapeutic hypothermia. TH achieved with this protocol was
associated with a significant reduction in hospital mortality.
PMID- 22046540
TI - A brief training module improves recognition of echocardiographic wall-motion
abnormalities by emergency medicine physicians.
AB - Objective. Wall-motion abnormality on echocardiogram is more sensitive in
detecting cardiac ischemia than the electrocardiogram, but the use of bedside
echocardiography by emergency physicians (EPs) for this purpose does not appear
to be widespread, apparently due to limited data on proficiency of EPs for this
task. We sought to determine the effect of a brief training module on the ability
of EPs to recognize wall motion abnormalities on echocardiograms. Methods. We
developed a brief training and testing module and presented it to EPs. After
baseline testing of 15 echocardiograms, we presented the 30-minute training
module, and administered a new test of 15 different echocardiograms. Physicians
were asked to interpret the wall motion as normal or abnormal. Results. 35 EPs
over two separate sessions showed significant improvement recognition of wall
motion abnormalities after the brief training module. Median score on the
baseline test was 67%, interquartile range (IQR) 53% to 80%, while the median
score on the posttraining test was 87%, IQR 80% to 87%, P < .001, independent of
time in practice or prior training. Conclusion. With only brief training on how
to recognize wall motion abnormalities on echocardiograms, EPs showed significant
improvement in ability to identify wall motion abnormalities.
PMID- 22046541
TI - Is blood alcohol level a good predictor for injury severity outcomes in motor
vehicle crash victims?
AB - Experimental studies in animals suggest that alcohol may influence
pathophysiologic response to injury mechanisms. However, biological evidence for
the alcohol-injury severity relationship provides conflicting results. The
purpose of our retrospective cross-sectional study in 2,323 people was to assess
whether blood alcohol level (BAC) adversely influences injury severity in victims
of motor vehicle collisions (MVCs). We found no difference in mortality OR 1.09
(0.73-1.62), or length of hospital stay, and a trend for lower ISS score was
found in the high-alcohol group (P = 0.052). Furthermore, the high-alcohol group
demonstrated a lower adjusted rate of severe head injury OR 0.65 (0.48-0.87),
chest injury OR 0.58 (0.42-0.80), and serious extremity injury OR 0.10 (0.01
0.76). The findings of our study do not demonstrate a dose-response relationship
between alcohol consumption and injury severity in MVCs. This study implies that
higher BAC may lead to less severe injuries, without impacting mortality or
length of hospital stay, however, further research is required to elucidate the
nature of this relationship.
PMID- 22046542
TI - Incidental Findings on CT Scans in the Emergency Department.
AB - Objectives. Incidental findings on computed tomography (CT) scans are common. We
sought to examine rates of findings and disclosure among discharged patients who
received a CT scan in the ED. Methods. Retrospective chart review (Aug-Oct 2009)
of 600 patients age 18 and older discharged home from an urban Level 1 trauma
center. CT reports were used to identify incidental findings and discharge
paperwork was used to determine whether the patient was informed of these
findings. Results. There were 682 CT scans among 600 patients: 199 Abdomen &
Pelvis, 405 Head, and 78 Thorax. A total of 348 incidental findings were
documented in 228/682 (33.4%) of the scans, of which 34 (9.8%) were reported to
patients in discharge paperwork. Patients with 1 incidental finding were less
likely to receive disclosure than patients with 2 or more (P = .010). Patients
age <60 were less likely to have incidental findings (P < .001). There was no
significant disclosure or incidental finding difference by gender. Conclusions.
While previous research suggests that CT incidental findings are often benign,
reporting to patients is recommended but this is rarely happening.
PMID- 22046543
TI - Seatbelt injury causing small bowel devascularisation: case series and review of
the literature.
AB - The use of seatbelts has increased significantly in the last twenty years,
leading to a decrease in mortality from road traffic accidents (RTA). However,
this increase in seatbelt use has also led to a change in the spectrum of
injuries from RTA; abdominal injuries, particularly intestinal injuries have
dramatically increased with the routine use of seatbelts. Such intestinal
injuries frequently result from improper placement of the "lap belt". We present
3 cases in which passengers wearing a seatbelt sustained significant
devascularisation injuries to the small bowel requiring emergency surgical
intervention. A high index of suspicion is crucial in such cases to prevent
delays in diagnosis that can lead to severe complications and adverse outcomes.
It is evident that while advocating seatbelt use, the importance of education in
correct seatbelt placement should also be a focus of public health strategies to
reduce RTA morbidity and mortality.
PMID- 22046544
TI - Diffusion of cardiopulmonary resuscitation training to chinese immigrants with
limited english proficiency.
AB - Cardiopulmonary resuscitation (CPR) is an effective intervention for prehospital
cardiac arrest. Despite all available training opportunities for CPR, disparities
exist in participation in CPR training, CPR knowledge, and receipt of bystander
CPR for certain ethnic groups. We conducted five focus groups with Chinese
immigrants who self-reported limited English proficiency (LEP). A bilingual
facilitator conducted all the sessions. All discussions were taped, recorded,
translated, and transcribed. Transcripts were analyzed by content analysis guided
by the theory of diffusion. The majority of participants did not know of CPR and
did not know where to get trained. Complexity of CPR procedure, advantages of
calling 9-1-1, lack of confidence, and possible liability discourage LEP
individuals to learn CPR. LEP individuals welcome simplified Hands-Only CPR and
are willing to perform CPR with instruction from 9-1-1 operators. Expanding the
current training to include Hands-Only CPR and dispatcher-assisted CPR may
motivate Chinese LEP individuals to get trained for CPR.
PMID- 22046545
TI - Isolated transverse sacrum fracture: a case report.
AB - Sacral fracture commonly results from high-energy trauma. Most insufficiency
fractures of the sacrum are seen in women after the age of 70. Fractures of the
sacrum are rare and generally combined with a concomitant pelvic fracture.
Transverse sacral fractures are even less frequent which constitute only 3-5% of
all sacral fractures. This type of fractures provide a diagnostic challenge. We
report a unique case of isolated transverse fracture of sacrum in a young man
sustained low-energy trauma. The patient presented to our emergency department
after several hours of injury, and diagnosed by clinical features and
roentgenogram findings.
PMID- 22046546
TI - Vascular injury accompanying displaced proximal humeral fractures: two cases and
a review of the literature.
AB - We present two cases in which displaced proximal humeral fractures are
accompanied by vascular injury. These Injuries are very rare but severe and the
accompanying vascular impairment can have great clinical consequences. Therefore,
we try to emphasize on the importance of thorough and accurate diagnostics,
because it is obligatory for early diagnosis and improving the eventual outcome
of these injuries. The specific order in treatment (internal fixation first or
vascular repair first) depends on the severity of the accompanying vascular
injury. The increasing use of endovascular procedures to treat vascular lesions
is a very interesting development with several advantages, especially in elderly
and multimorbid patients.
PMID- 22046547
TI - Demographic analysis of emergency department patients at the ruijin hospital,
shanghai.
AB - Emergency medicine is an upcoming discipline that is still under development in
many countries. Therefore, it is important to gain insight into the organization
and patients presenting to the Emergency Department (ED). The aim of this cross
sectional study was to provide an epidemiological description of complaints and
referrals of the patients visiting the ED of the Ruijin Hospital in Shanghai,
China. A questionnaire was developed and completed for a convenience sample of
all patients presenting to the Triage Desk of the ED. The study was performed in
June 2008. A total of 2183 questionnaires were completed. The most common
complaints were fever (15%), stomach/abdominal pain (15%), vertigo/dizziness
(11%), and cough (10%). Following triage, patients were predominantly referred to
an internist (41%), neurologist (14%), pulmonologist (11%), or general surgeon
(9%). This study provides a better understanding of the reason for the ED visit
and the triage system at the ED of the Ruijin Hospital. The results can be used
in order to improve facilities appropriate for the specific population in the ED.
PMID- 22046548
TI - Lunar tractive forces and renal stone incidence.
AB - Background. Several factors are implicated in renal stone formation and peak
incidence of renal colic admissions to emergency departments (ED). Little is
known about the influence of potential environmental triggers such as lunar
gravitational forces. We conducted a retrospective study to test the hypothesis
that the incidence of symptomatic renal colics increases at the time of the full
and new moon because of increased lunar gravitational forces. Methods. We
analysed 1500 patients who attended our ED between 2000 and 2010 because of
nephrolithiasis-induced renal colic. The lunar phases were defined as full moon
+/- 1 day, new moon +/- 1 day, and the days in-between as "normal" days. Results.
During this 11-year period, 156 cases of acute nephrolithiasis were diagnosed at
the time of a full moon and 146 at the time of a new moon (mean of 0.4 per day
for both). 1198 cases were diagnosed on "normal" days (mean 0.4 per day). The
incidence of nephrolithiasis in peak and other lunar gravitational phases, the
circannual variation and the gender-specific analysis showed no statistically
significant differences. Conclusion. In this adequate powered longitudinal study,
changes in tractive force during the different lunar phases did not influence the
incidence of renal colic admissions in emergency department.
PMID- 22046549
TI - Blunt cardiac injury in trauma patients with thoracic aortic injury.
AB - Trauma patients with thoracic aortic injury (TAI) suffer blunt cardiac injury
(BCI) at variable frequencies. This investigation aimed to determine the
frequency of BCI in trauma patients with TAI and compare with those without TAI.
All trauma patients with TAI who had admission electrocardiography (ECG) and
serum creatine kinase-MB (CK-MB) from January 1999 to May 2009 were included as a
study group at a level I trauma center. BCI was diagnosed if there was a positive
ECG with either an elevated CK-MB or abnormal echocardiography. There were 26
patients (19 men, mean age 45.1 years, mean ISS 34.4) in the study group; 20 had
evidence of BCI. Of 52 patients in the control group (38 men, mean age 46.9
years, mean ISS 38.7), eighteen had evidence of BCI. There was a significantly
higher rate of BCI in trauma patients with TAI versus those without TAI (77%
versus 35%, P < 0.001).
PMID- 22046550
TI - The role of thrombelastography in multiple trauma.
AB - Hemorrhage and traumatic coagulopathyis are major causes of early death in
multiply injured patients. Thrombelastography (TEG) seems to be a fast and
accurate coagulation test in trauma care. We suggest that multiply injured trauma
patients would benefit the most from an early assessment of coagulation by TEG,
mainly RapidTEG, to detect an acute traumatic coagulopathy and especially primary
fibrinolysis, which is related with high mortality. This review gives an overview
on TEG and its clinical applications.
PMID- 22046551
TI - Impact of 2004 tsunami in the islands of Indian ocean: lessons learned.
AB - Tsunami of 2004, caused by a 9.0 magnitude earthquake, is the most devastating
tsunami in modern times, affecting 18 countries in Southeast Asia and Southern
Africa, killing more than 250,000 people in a single day, and leaving more than
1.7 million homeless. However, less reported, albeit real, is its impact in the
islands of the Indian Ocean more than 1,000 miles away from its epicenter. This
is the first peer-reviewed paper on the 2004 tsunami events specifically in the
eleven nations bordering the Indian Ocean, as they constitute a region at risk,
due to the presence of tectonic interactive plate, absence of a tsunami warning
system in the Indian Ocean, and lack established communication network providing
timely information to that region. Our paper has a dual objective: the first
objective is to report the 2004 tsunami event in relation to the 11 nations
bordering the Indian Ocean. The second one is to elaborate on lessons learned
from it from national, regional, and international disaster management programs
to prevent such devastating consequences of tsunami from occurring again in the
future.
PMID- 22046552
TI - Skull base osteomyelitis in the emergency department: a case report.
AB - Skull base osteomyelitis (SBO) is a rare clinical presentation and usually occurs
as a complication of trauma or sinusitis. A 5-year-old child presented to the
emergency department with a three-week history of fever associated with
drowsiness and left parietal headache, and a week's history of swelling on the
left frontoparietal soft tissue. He had suffered a penetrating scalp injury four
month ago. On physical examination, there was a tender swelling with purulent
stream on the lateral half of his scalp. His vital signs are within normal
limits. Plain X-ray of the skull showed a lytic lesion on the left frontoparietal
bone. A cranial computed tomography (CT) scan demonstrated a large subgaleal
abscess at the left frontoparietal region. SBO possesses a high morbidity and
mortality; therefore, prompt diagnosis and appropriate treatment are mandatory to
prevent further complications and to reduce morbidity and mortality
significantly.
PMID- 22046553
TI - Perceived differences in the management of mental health patients in remote and
rural australia and strategies for improvement: findings from a national
qualitative study of emergency clinicians.
AB - Introduction. We aimed to describe perceptions of Australian emergency clinicians
of differences in management of mental health patients in rural and remote
Australia compared with metropolitan hospitals, and what could be improved.
Methods. Descriptive exploratory study using semi-structured telephone interviews
of doctors and nurses in Australian emergency departments (EDs), stratified to
represent states and territories and rural or metropolitan location. Content
analysis of responses developed themes and sub-themes. Results. Of 39 doctors and
32 nurses responding to email invitation, 20 doctors and 16 nurses were
interviewed. Major themes were resources/environment, staff and patient issues.
Clinicians noted lack of access in rural areas to psychiatric support services,
especially alcohol and drug services, limited referral options, and a lack of
knowledge, understanding and acceptance of mental health issues. The clinicians
suggested resource, education and guideline improvements, wanting better access
to mental health experts in rural areas, better support networks and visiting
specialist coverage, and educational courses tailored to the needs of rural
clinicians. Conclusion. Clinicians managing mental health patients in rural and
remote Australian EDs lack resources, support services and referral capacity, and
access to appropriate education and training. Improvements would better enable
access to support and referral services, and educational opportunities.
PMID- 22046554
TI - Measuring quality in emergency medical services: a review of clinical performance
indicators.
AB - Measuring quality in Emergency Medical Services (EMSs) systems is challenging.
This paper reviews the current approaches to measuring quality in health care and
EMS with a focus on currently used clinical performance indicators in EMS systems
(US and international systems). The different types of performance indicators,
the advantages and limitations of each type, and the evidence-based prehospital
clinical bundles are discussed. This paper aims at introducing emergency
physicians and health care providers to quality initiatives in EMS and serves as
a reference for tools that EMS medical directors can use to launch new or modify
existing quality control programs in their systems.
PMID- 22046555
TI - Molecular Network Associated with MITF in Skin Melanoma Development and
Progression.
AB - Various environmental and genetic factors affect the development and progression
of skin cancers including melanoma. Melanoma development is initially triggered
by environmental factors including ultraviolet (UV) light, and then
genetic/epigenetic alterations occur in skin melanocytes. These first triggers
alter the conditions of numerous genes and proteins, and they induce and/or
reduce gene expression and activate and/or repress protein stability and
activity, resulting in melanoma progression. Microphthalmia-associated
transcription factor (MITF) is a master regulator gene of melanocyte development
and differentiation and is also associated with melanoma development and
progression. To find better approaches to molecular-based therapies for patients,
understanding MITF function in skin melanoma development and progression is
important. Here, we review the molecular networks associated with MITF in skin
melanoma development and progression.
PMID- 22046556
TI - Bone marrow stem cell derived paracrine factors for regenerative medicine:
current perspectives and therapeutic potential.
AB - During the past several years, there has been intense research in the field of
bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into
clinical setting. Although a lot has been accomplished, plenty of challenges lie
ahead. Furthermore, there is a growing body of evidence showing that
administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the
beneficial effects observed after stem cell therapy. BMSCs produce a wide range
of cytokines and chemokines that have, until now, shown extensive therapeutic
potential. These paracrine mechanisms could be as diverse as stimulating receptor
mediated survival pathways, inducing stem cell homing and differentiation or
regulating the anti-inflammatory effects in wounded areas. The current review
reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many
logistical and technical issues regarding cell therapy and evaluates its future
potential as an effective regenerative therapy.
PMID- 22046557
TI - Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating
Cells in NOD/SCID versus NOD/SCID/gamma chain Mice.
AB - Humanized bone-marrow xenograft models that can monitor the long-term impact of
gene-therapy strategies will help facilitate evaluation of clinical utility. The
ability of the murine bone-marrow microenvironment in NOD/SCID versus
NOD/SCID/gamma chain(null) mice to support long-term engraftment of MGMT(P140K)
transduced human-hematopoietic cells following alkylator-mediated in vivo
selection was investigated. Mice were transplanted with MGMT(P140K)-transduced
CD34(+) cells and transduced cells selected in vivo. At 4 months after
transplantation, levels of human-cell engraftment, and MGMT(P140K)-transduced
cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle-
and drug-treated mice. In secondary transplants, although equal numbers of
MGMT(P140K)-transduced human cells were transplanted, engraftment was
significantly higher in NOD/SCID/gamma chain(null) mice compared to NOD/SCID mice
at 2 months after transplantation. These data indicate that reconstitution of
NOD/SCID/gamma chain(null) mice with human-hematopoietic cells represents a more
promising model in which to test for genotoxicity and efficacy of strategies that
focus on manipulation of long-term repopulating cells of human origin.
PMID- 22046558
TI - Immune recovery after cyclophosphamide treatment in multiple myeloma: implication
for maintenance immunotherapy.
AB - Multiple myeloma (MM) is a progressive B-lineage neoplasia characterized by
clonal proliferation of malignant plasma cells. Increased numbers of regulatory T
cells (Tregs) were determined in mouse models and in patients with MM, which
correlated with disease burden. Thus, it became rational to target Tregs for
treating MM. The effects of common chemotherapeutic drugs on Tregs are reviewed
with a focus on cyclophosphamide (CYC). Studies indicated that selective
depletion of Tregs may be accomplished following the administration of a low-dose
CYC. We report that continuous nonfrequent administrations of CYC at low doses
block the renewal of Tregs in MM-affected mice and enable the restoration of an
efficient immune response against the tumor cells, thereby leading to prolonged
survival and prevention of disease recurrence. Hence, distinctive time-schedule
injections of low-dose CYC are beneficial for breaking immune tolerance against
MM tumor cells.
PMID- 22046559
TI - Haploidentical hematopoietic stem-cell transplantation in adults.
AB - Haploidentical hematopoietic stem-cell transplantation is an alternative
transplant strategy for patients without an HLA-matched donor. Still, only half
of patients who might benefit from transplantation are able to find an HLA
matched related or unrelated donor. Haploidentical donor is readily available for
many patients in need of immediate stem-cell transplantation. Historical
experience with haploidentical stem-cell transplantation has been characterised
by a high rejection rate, graft-versus-host disease, and transplant-related
mortality. Important advances have been made in this field during the last 20
years. Many drawbacks of haploidentical transplants such as graft failure and
significant GVHD have been overcome due to the development of new extensive T
cell depletion methods with mega dose stem-cell administration. However,
prolonged immune deficiency and an increased relapse rate remain unresolved
problems of T cell depletion. New approaches such as partial ex vivo or in vivo
alloreactive T cell depletion and posttransplant cell therapy will allow to
improve immune reconstitution in haploidentical transplants. Results of
unmanipulated stem-cell transplantation with using ATG and combined
immunosuppression in mismatched/haploidentical transplant setting are promising.
This paper focuses on recent advances in haploidentical hematopoietic stem-cell
transplantation for hematologic malignancies.
PMID- 22046560
TI - Paracrine molecules of mesenchymal stem cells for hematopoietic stem cell niche.
AB - Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult
stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate
and enhance the proliferation of HSCs by secreting regulatory molecules and
cytokines, providing a specialized microenvironment for controlling the process
of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche,
maintain the stemness and proliferation of HSCs, and support HSC transplantation.
PMID- 22046561
TI - Breast cancer stem cells survive periods of farnesyl-transferase inhibitor
induced dormancy by undergoing autophagy.
AB - A cancer stem cell has been defined as a cell within a tumor that possesses the
capacity to self-renew and to cause the heterogeneous lineages of cancer cells
that comprise the tumor. These tumor-forming cells could hypothetically originate
from stem, progenitor, or differentiated cells. Previously, we have shown that
breast cancer cells with low metastatic potential can be induced into a
reversible state of dormancy by farnesyl transferase inhibitors (FTIs). Dormancy
was induced by changes in RhoA and RhoC GTPases. Specifically, RhoA was found to
be hypoactivated while RhoC was hyperactivated. In the current study we
demonstrate that these dormant cells also express certain known stem cell markers
such as aldehyde dehydrogenase I (ALDHI) and cluster of differentiation 44
(CD44). We also show that autophagy markers Atg5, Atg12, and LC3-B are expressed
in these dormant stem cell-like breast cancer cells. Inhibiting autophagy by
inhibitor 3-methyladenine (3-MA) blocked the process of autophagy reversing the
dormant phenotype. Further, we show that c-jun NH2 terminal kinase (JNK/SAPK) is
upregulated in these dormant stem cell-like breast cancer cells and is
responsible for increasing autophagy.
PMID- 22046562
TI - One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary
Injection of CD133 Bone Marrow Stem Cells to Placebo in Patients after Acute
Myocardial Infarction and Left Ventricular Dysfunction.
AB - Bone marrow stem cell therapy has emerged as a promising approach to improve
healing of the infarcted myocardium. Despite initial excitement, recent clinical
trials using non-homogenous stem cells preparations showed variable and mixed
results. Selected CD133(+) hematopoietic stem cells are candidate cells with high
potential. Herein, we report the one-year safety analysis on the initial 20
patients enrolled in the COMPARE-AMI trial, the first double-blind randomized
controlled trial comparing the safety, efficacy, and functional effect of
intracoronary injection of selected CD133(+) cells to placebo following acute
myocardial infarction with persistent left ventricular dysfunction. At one year,
there is no protocol-related complication to report such as death, myocardial
infarction, stroke, or sustained ventricular arrhythmia. In addition, the left
ventricular ejection fraction significantly improved at four months as compared
to baseline and remained significantly higher at one year. These data indicate
that in the setting of the COMPARE-AMI trial, the intracoronary injection of
selected CD133(+) stem cells is secure and feasible in patients with left
ventricle dysfunction following acute myocardial infarction.
PMID- 22046563
TI - Recent advances in the pathogenesis and management of cast nephropathy (myeloma
kidney).
AB - Multiple myeloma is an incurable plasma cell malignancy that is often accompanied
by renal failure; there are a number of potential causes of this, of which cast
nephropathy is the most important. Renal failure is highly significant in
myeloma, as patient survival can be stratified by the severity of the renal
impairment. Consequently, there is an ongoing focus on the pathological basis of
cast nephropathy and the optimal treatment regimens in this setting, including
effective chemotherapy regimens to reduce light chain production and emerging
extracorporeal techniques to remove circulating light chains. This paper bridges
recent advances in the pathogenesis and management of cast nephropathy in
multiple myeloma.
PMID- 22046564
TI - Signaling proteins and transcription factors in normal and malignant early B cell
development.
AB - B cell development starts in bone marrow with the commitment of hematopoietic
progenitors to the B cell lineage. In murine models, the IL-7 and preBCR
receptors, and the signaling pathways and transcription factors that they
regulate, control commitment and maintenance along the B cell pathway. E2A, EBF1,
PAX5, and Ikaros are among the most important transcription factors controlling
early development and thereby conditioning mice homeostatic B cell lymphopoiesis.
Importantly, their gain or loss of function often results in malignant
development in humans, supporting conserved roles for these transcription
factors. B cell acute lymphoblastic leukemia is the most common cause of
pediatric cancer, and it is characterized by unpaired early B cell development
resulting from genetic lesions in these critical signaling pathways and
transcription factors. Fine mapping of these genetic abnormalities is allowing
more specific treatments, more accurately predicting risk profiles for this
disease, and improving survival rates.
PMID- 22046565
TI - Factors influencing the abundance of the side population in a human myeloma cell
line.
AB - Side population (SP) refers to a group of cells, which is capable to efflux
Hoechst 33342, a DNA-binding dye. SP cells exist both in normal and tumor
tissues. Although SP abundance has been used as an indicator for disease
prognostic and drug screening in many research projects, few studies have
systematically examined the factors influencing SP analysis. In this study we aim
to develop a more thorough understanding of the multiple factors involved in SP
analysis including Hoechst 33342 staining and cell culture. RPMI-8226, a high SP
percentage (SP%) human myeloma cell line was employed here. The results showed
that SP% was subject to staining conditions including: viable cell proportion,
dye concentration, staining cell density, incubation duration, staining volume,
and mix interval. In addition, SP% was highest in day one after passage, while
dropped steadily over time. This study shows that both staining conditions and
culture duration can significantly affect SP%. In this case, any conclusions
based on SP% should be interpreted cautiously. The relation between culture
duration and SP% suggests that the incidence of SP cells may be related to cell
proliferation and cell cycle phase. Maintaining these technical variables
consistently is essential in SP research.
PMID- 22046566
TI - Future perspectives: therapeutic targeting of notch signalling may become a
strategy in patients receiving stem cell transplantation for hematologic
malignancies.
AB - The human Notch system consists of 5 ligands and 4 membrane receptors with
promiscuous ligand binding, and Notch-initiated signalling interacts with a wide
range of other intracellular pathways. The receptor signalling seems important
for regulation of normal and malignant hematopoiesis, development of the cellular
immune system, and regulation of immune responses. Several Notch-targeting agents
are now being developed, including natural receptor ligands, agonistic and
antagonistic antibodies, and inhibitors of intracellular Notch-initiated
signalling. Some of these agents are in clinical trials, and several therapeutic
strategies seem possible in stem cell recipients: (i) agonists may be used for
stem cell expansion and possibly to enhance posttransplant lymphoid
reconstitution; (ii) receptor-specific agonists or antagonists can be used for
immunomodulation; (iii) Notch targeting may have direct anticancer effects.
Although the effects of therapeutic targeting are difficult to predict due to
promiscuous ligand binding, targeting of this system may represent an opportunity
to achieve combined effects with earlier posttransplant reconstitution,
immunomodulation, or direct anticancer effects.
PMID- 22046567
TI - Hyperbaric oxygen therapy as a sole agent is not immunosuppressant in a highly
immunogenic mouse model.
AB - Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions,
may also have immunosuppressive effects and could be used for prevention or
treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then
we hypothesize that HBO therapy will delay the T-cell mediated skin graft
rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA
(H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa
oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4
per cage or separately, to prevent friction and mechanical factors that may
affect graft survival. Skin grafts were assessed daily. Results. There was no
difference in length of graft survival between mice that received either regimens
of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO
therapy, as a sole agent, did not delay skin graft rejection in a highly
immunogenic mouse model.
PMID- 22046568
TI - Multiple myeloma: a review of imaging features and radiological techniques.
AB - The recently updated Durie/Salmon PLUS staging system published in 2006
highlights the many advances that have been made in the imaging of multiple
myeloma, a common malignancy of plasma cells. In this article, we shall focus
primarily on the more sensitive and specific whole-body imaging techniques,
including whole-body computed tomography, whole-body magnetic resonance imaging,
and positron emission computed tomography. We shall also discuss new and emerging
imaging techniques and future developments in the radiological assessment of
multiple myeloma.
PMID- 22046570
TI - A Case of Monoclonal Lymphoplasmacytosis of the Bone Marrow with IgM-Positive
Russell Bodies.
AB - A 71-year-old Japanese male patient infected with HCV was diagnosed with
thrombocytopenia. Histological examination of the bone marrow aspirate showed
numerous lymphoid aggregates with Russell bodies. Immunohistochemistry and flow
cytometric analysis demonstrated clonal expansion of CD5+ CD23+ B cells. Russell
bodies were positive for IgM and lambda immunoglobulin light chain. The patient
also underwent gastric biopsy, which revealed Helicobacter pylori (HP) infection.
Subsequent eradication of the bacteria resulted in improvement of his
thrombocytopenia. The clinical course remained uneventful at 15-month follow-up,
consistent with monoclonal B-cell lymphocytosis. The observed clonal expansion
with plasmacytic differentiation may have occurred under the influence of HCV
with HP infection.
PMID- 22046569
TI - Oncolytic virotherapy for multiple myeloma: past, present, and future.
AB - Multiple myeloma (MM) is a B-cell malignancy that is currently felt to be
incurable. Despite recently approved novel targeted treatments such as
lenalidomide and bortezomib, most MM patients' relapse is emphasizing the need
for effective and well-tolerated therapies for this deadly disease. The use of
oncolytic viruses has garnered significant interest as cancer therapeutics in
recent years, and are currently under intense clinical investigation. Both
naturally occurring and engineered DNA and RNA viruses have been investigated
preclinically as treatment modalities for several solid and hematological
malignancies. Presently, only a genetically modified measles virus is in human
clinical trials for MM. The information obtained from this and other future
clinical trials will guide clinical application of oncolytic viruses as
anticancer agents for MM. This paper provides a timely overview of the history of
oncolytic viruses for the treatment of MM and future strategies for the
optimization of viral therapy for this disease.
PMID- 22046571
TI - Transplantation for congenital bone marrow failure syndromes.
AB - Congenital bone marrow failure syndromes (BMFSs) are relatively rare disorders
characterized by aberrant development in one or more hematopoietic lineages.
Genetic alterations have now been identified in most of these disorders although
the exact role of the molecular defects has yet to be elucidated. Most of these
diseases are successfully managed with supportive care, however, treatment
refractoriness and disease progression-often involving malignant transformation
may necessitate curative treatment with hematopoietic stem cell transplantation.
Due to the underlying molecular defects, the outcome of transplantation for BMFS
may be dramatically different than those associated with transplantation for more
common diseases, including leukemia. Given recent improvements in survival and
molecular diagnosis of bone marrow failure syndrome patients presenting at adult
ages without physical stigmata, it is important for both pediatric and adult
hematologists to be aware of the possible diagnosis of BMF syndromes and the
unique approaches required in treating such patients.
PMID- 22046572
TI - Antibody-based therapies in multiple myeloma.
AB - The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical
development of monoclonal antibodies (mAbs) targeting either MM cells or cells of
the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors,
therapeutic mAbs present the potential to specifically target tumor cells and
directly induce an immune response to lyse tumor cells. Unique immune-effector
mechanisms are only triggered by therapeutic mAbs but not by small molecule
targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause
immunogenicity, the advancement of genetic recombination for humanizing rodent
mAbs has allowed large-scale production and designation of mAbs with better
affinities, efficient selection, decreasing immunogenicity, and improved effector
functions. These advancements of antibody engineering technologies have largely
overcome the critical obstacle of antibody immunogenicity and enabled the
development and subsequent Food and Drug Administration (FDA) approval of
therapeutic Abs for cancer and other diseases.
PMID- 22046573
TI - Innovative analyses support a role for DNA damage and an aberrant cell cycle in
myelodysplastic syndrome pathogenesis.
AB - We used flow cytometry to analyze the cell cycle, DNA damage, and apoptosis in
hematopoietic subsets in MDS marrow. Subsets were assigned using CD45, side
scatter, CD34, and CD71. Cell cycle fractions were analyzed using DRAQ 5 (DNA
content) and MPM-2 (mitoses). DNA damage was assessed using p-H2A.X, and
apoptosis using Annexin V. Compared to controls, MDS patients demonstrated no
increased mitoses in erythroid, myeloid, or CD34+ cells. Myeloid progenitors
demonstrated increased G2 cells, which with no increased mitoses suggested
delayed passage through G2. Myeloid progenitors demonstrated increased p-H2A.X,
consistent with DNA damage causing this delay. Annexin V reactivity was
equivalent in MDS and controls. Results for each parameter varied among
hematopoietic compartments, demonstrating the need to analyze compartments
separately. Our results suggest that peripheral cytopenias in MDS are due to
delayed cell cycle passage of marrow progenitors and that this delayed passage
and leukemic progression derive from excessive DNA damage.
PMID- 22046574
TI - T-cell costimulatory molecules in acute-graft-versus host disease: therapeutic
implications.
AB - Acute Graft-versus-host disease (GVHD) is a major complication after allogeneic
hematopoietic stem cell transplantation. Although this process is thought to
consist of several phases, T-cell activation plays a critical role in the
pathogenesis of acute GVHD. To become efficient effectors, T-cells require
additional costimulation after T-cell receptor signaling. A number of molecules
are involved in costimulation of T-cells such as CD28, CD40L, CD30, OX40, 4-1BB,
ICOS, and LIGHT. The system is regulated by inhibitory molecules, CTLA-4, and PD
1. There is experimental evidence that those molecules are implicated in the
pathogenesis of GHVD. We describe how these molecules are involved in acute GVHD
and how the blockade of costimulatory molecules may have potential implications
for the treatment of patients with acute GVHD.
PMID- 22046575
TI - Operative outcomes for cervical myelopathy and radiculopathy.
AB - Cervical spondylotic myelopathy and radiculopathy are common disorders which can
lead to significant clinical morbidity. Conservative management, such as physical
therapy, cervical immobilisation, or anti-inflammatory medications, is the
preferred and often only required intervention. Surgical intervention is reserved
for those patients who have intractable pain or progressive neurological
symptoms. The goals of surgical treatment are decompression of the spinal cord
and nerve roots and deformity prevention by maintaining or supplementing spinal
stability and alleviating pain. Numerous surgical techniques exist to alleviate
symptoms, which are achieved through anterior, posterior, or circumferential
approaches. Under most circumstances, one approach will produce optimal results.
It is important that the surgical plan is tailored to address each individual's
unique clinical circumstance. The objective of this paper is to analyse the major
surgical treatment options for cervical myelopathy and radiculopathy focusing on
outcomes and complications.
PMID- 22046576
TI - Rap2A Is Upregulated in Invasive Cells Dissected from Follicular Thyroid Cancer.
AB - The development of molecular biomarkers (BMs) of follicular thyroid carcinoma is
aimed at advancing diagnosis of follicular neoplasm, as histological examination
of those tumors does not lend itself to definitive diagnosis of carcinoma. We
assessed the relative levels of expression of 6 genes: CCND2, PCSK2, PLAB, RAP2A,
TSHR, and IGF-1R in archived thyroid tissue. The quantitative real-time PCR
analysis revealed a significant change in 3 genes: PSCK2 (a 22.4-fold decrease, P
= 2.81E - 2), PLAB (an 8.3-fold increase, P = 9.81E - 12), and RAP2A (a 6.3-fold
increase, P = 9.13E - 10) in carcinoma compared with adenoma. Expression of PCSK2
was equally low, PLAB was equally high, whereas RAP2A expression was
significantly higher (25.9-fold, P = 0.039) in microdissected carcinoma cells
that have invaded through the thyroid capsule and entered blood vessels than in
thyroid tumor cells growing under the capsule. Thus, RAP2A appeared as a unique
and worthy of further evaluation candidate BM associated with invasion of thyroid
follicular cells.
PMID- 22046577
TI - A preliminary report on disordered speech with deep brain stimulation in
individuals with Parkinson's disease.
AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proven
effective in treating the major motor symptoms of advanced Parkinson's disease
(PD). The aim of this study was to learn which laryngeal and articulatory
acoustic features changed in patients who were reported to have worse speech with
stimulation. Six volunteers with PD who had bilateral STN electrodes were
recorded with DBS turned on or off. Perceptual ratings reflected poorer speech
performance with DBS on. Acoustic measures of articulation (corner vowel
formants, diphthong slopes, and a spirantization index) and phonation
(perturbation, long-term average spectrum) as well as verbal fluency scores
showed mixed results with DBS. Some speakers improved while others became worse
on individual measures. The magnitude of DBS effects was not predictable based on
the patients' demographic characteristics. Future research involving adjustments
to stimulator settings or electrode placement may be beneficial in limiting the
negative effects of DBS on speech.
PMID- 22046578
TI - The PIT: SToPP Trial-A Feasibility Randomised Controlled Trial of Home-Based
Physiotherapy for People with Parkinson's Disease Using Video-Based Measures to
Preserve Assessor Blinding.
AB - Purpose. To trial four-week's physiotherapy targeting chair transfers for people
with Parkinson's disease (PwPD) and explore the feasibility of reliance on remote
outcome measurement to preserve blinding. Scope. We recruited 47 PwPD and
randomised 24 to a focused home physiotherapy programme (exercise, movement
strategies, and cueing) and 23 to a control group. We evaluated transfers (plus
mobility, balance, posture, and quality of life) before and after treatment and
at followup (weeks 0, 4, 8, and 12) from video produced by, and questionnaires
distributed by, treating physiotherapists. Participants fed back via end-of-study
questionnaires. Thirty-five participants (74%) completed the trial. Excluding
dropouts, 20% of questionnaire data and 9% of video data were missing or
unusable; we had to evaluate balance in situ. We noted trends to improvement in
transfers, mobility, and balance in the physiotherapy group not noted in the
control group. Participant feedback was largely positive and assessor blinding
was maintained in every case. Conclusions. Intense, focused physiotherapy at home
appears acceptable and likely to bring positive change in those who can
participate. Remote outcome measurement was successful; questionnaire followup
and further training in video production would reduce missing data. We advocate a
fully powered trial, designed to minimise dropouts and preserve assessor
blinding, to evaluate this intervention.
PMID- 22046579
TI - Capsaicin-sensitive afferentation represents an indifferent defensive pathway
from eradication in patients with H. pylori gastritis.
AB - AIM: To study the role of capsaicin-sensitive afferent nerves in Helicobacter
pylori (H. pylori) positive chronic gastritis before and after eradication.
METHODS: Gastric biopsy samples were obtained from corpus and antrum mucosa of 20
healthy human subjects and 18 patients with H. pylori positive chronic gastritis
(n = 18) before and after eradication. Traditional gastric mucosal histology (and
Warthin-Starry silver impregnation) and special histochemical examinations were
carried out. Immunohistochemistry for capsaicin receptor (TRVP1), calcitonin gene
related peptide (CGRP) and substance P (SP) were carried out by the labeled
polymer immunohistological method (Lab Vision Co., USA) using polyclonal rabbit
and rat monoclonal antibodies (Abcam Ltd., UK). RESULTS: Eradication treatment
was successful in 16 patients (89%). Seven patients (7/18, 39%) remained with
moderate complaints, meanwhile 11 patients (11/28, 61%) had no complaints. At
histological evaluation, normal gastric mucosa was detected in 4 patients after
eradication treatment (4/18, 22%), and moderate chronic gastritis could be seen
in 14 (14/18, 78%) patients. Positive immuno-staining for capsaicin receptor was
seen in 35% (7/20) of controls, 89% (16/18, P < 0.001) in patients before and 72%
(13/18, P < 0.03) after eradication. CGRP was positive in 40% (8/20) of controls,
and in 100% (18/18, P < 0.001) of patients before and in 100% (18/18, P < 0.001)
after eradication. The immune-staining of gastric mucosa for substance-P was
positive in 25% (5/20) of healthy controls, and in 5.5% (3/18, P > 0.05) of
patients before and in 0% of patients (0/18, P > 0.05) after H. pylori
eradication. CONCLUSION: Distibution of TRVP1 and CGRP is altered during the
development of H. pylori positive chronic gastritis. The immune-staining for
TRVP1, CGRP and SP rwemained unchanged before and after H. pylori eradication
treatment. The capsaicin-sensitive afferentation is an independent from the
eradication treatment. The 6 wk time period might not be enough time for the
restituion of chronic H. pylori positive chronic gastritis. The H. pylori
infection might not represent the main pathological factor in the development of
chronic gastritis.
PMID- 22046580
TI - Contribution of G71R mutation to Gilbert's syndrome phenotype in a Greek patient:
A case report.
AB - Gilbert's syndrome is characterized by a benign indirect hyperbilirubinemia. It
has often been underestimated and undiagnosed because of its mild symptoms;
although it is not as rare as was once believed when its frequency was estimated
using data originating from biochemical tests. Based on molecular techniques, the
occurrence of Gilbert's syndrome has changed, increasing to 10% in the Caucasian
population. This molecular defect was described, by Bosma et al, in 1995, and
affects the promoter region of the UGT 1A1 gene. In this case report, our aim is
to present a new combination of two molecular defects in a Greek patient with
Gilbert's syndrome. A 13-year-old Greek girl was examined for Gilbert's syndrome
using molecular techniques, and an uncommon genotype was revealed comprising the
rare mutation G71R in trans with A(TA)7TAA motif. The G71R mutation according to
the literature, as well as our epidemiological data, is rare in Caucasians, while
it is common in Asian populations. This is the first case study in the Greek
population to report a new genotype for Gilbert's syndrome manifestation in the
Caucasian population.
PMID- 22046581
TI - Investigation of the toxic effect of a QDs heterojunction on the interactions
between small molecules and plasma proteins by fluorescence and resonance light
scattering spectra.
AB - The effect of a ZnO#ZnS QDs heterojunction (O#SQDs) on the binding affinities of
flavonoid glycosides for bovine serum albumin (BSA) was investigated. The
fluorescence intensities of BSA decreased remarkably with increasing
concentration of O#SQDs. The magnitudes of the binding constants of flavonoid
glycosides for BSA in the presence of O#SQDs were in the range of 10(5)-10(7) L
mol(-1), and the number of binding sites per BSA (n) was determined as 1.24 +/-
0.17. O#SQDs increased the affinities of flavonoid glycosides for BSA by about
2.96% to 114.68% depending on their structures. O#SQDs in blood will enhance the
transportation of flavonoid glycosidegs in blood and improve their pharmacology
effects. From this point, O#SQDs are a perfect candidate for flavonoid glycosides
delivery applications.
PMID- 22046582
TI - Differentiating intrinsic SERS spectra from a mixture by sampling induced
composition gradient and independent component analysis.
AB - By generating a composition gradient on a highly uniform SERS substrate and
applying independent component analysis, we demonstrate that one can extract the
intrinsic SERS spectrum of individual components from SERS spectra obtained from
a two-component mixture.
PMID- 22046583
TI - Micromechanical measurement of AChBP binding for label-free drug discovery.
AB - A potential binding assay based on binding-driven micromechanical motion is
described. Acetylcholine binding protein (AChBP) was used to modify a
microcantilever. The modified microcantilever was found to bend on application of
the naturally occurring agonist (acetylcholine) or the antagonist (nicotine and d
tubocurarine). Control experiments show that microcantilevers modified without
AChBP do not respond to acetylcholine, nicotine, and d-tubocurarine. K(d) values
obtained for acetylcholine, nicotine, and d-tubocurarine are similar to those
obtained from radio-ligand binding assays. These results suggest that the
microcantilever system has potential for use in label free, drug screening
applications.
PMID- 22046584
TI - Electrocatalytic reaction of hydrogen peroxide and NADH based on poly(neutral
red) and FAD hybrid film.
AB - A simple method to immobilize poly(neutral red) (PNR) and flavin adenine
dinucleotide (FAD) hybrid film (PNR/FAD) by cyclic voltammetry is proposed. The
PNR/FAD hybrid film can be easily prepared on an electrode surface involving
electropolymerization of neutral red (NR) monomers and the electrostatic
interaction between the positively charged PNR and the negatively charged FAD. It
exhibits electroactive, stable, surface-confined, pH-dependent, nano-sized, and
compatible properties. It provides good electrocatalytic properties to various
species. It shows a sensitivity of 5.4 MUA mM(-1) cm(-2) and 21.5 MUA mM(-1) cm(
2) for hydrogen peroxide (H(2)O(2)) and nicotinamide adenine dinucleotide (NADH)
with the linear range of 0.1 MUM-39 mM and 5 * 10(-5) to 2.5 * 10(-4) M,
respectively. It shows another linear range of 48.8-355.5 mM with the sensitivity
of 12.3 MUA mM(-1) cm(-2) for H(2)O(2). In particular, the PNR/FAD hybrid film
has potential to replace some hemoproteins to be a cathode of biofuel cells and
provide the biosensing system for glucose and ethanol.
PMID- 22046585
TI - Direct synthesis of pyrroles via a silver-promoted three-component reaction
involving unusual imidazole ring opening.
AB - A novel silver-promoted three-component reaction toward the synthesis of
multifunctionalized pyrroles has been developed. This reaction involves an
unusual imidazole ring decomposition, presumably via 1,5-isomerization and
subsequent hydrolysis.
PMID- 22046586
TI - A molecular chalice with hydrophobic walls and a hydrophilic rim: self-assembly
and complexation properties.
AB - We describe the synthesis of a diphenylglycoluril/dibenzo-crown-6 molecular
chalice, the self-assembly at the air/water interface and its complexation
properties in solution and at the water/chloroform interface.
PMID- 22046587
TI - Sorption and separation of CO2 via nanoscale AlO(OH) hollow spheres.
AB - The CO(2) uptake on nanoscale AlO(OH) hollow spheres (260 mg g(-1)) as a new
material is comparable to that on many metal-organic frameworks although their
specific surface area is much lower (530 m(2) g(!1)versus 1500-6000 m(2) g(!1)).
Suited temperature-pressure cycles allow for reversible storage and separation of
CO(2) while the CO(2) uptake is 4.3-times higher as compared to N(2).
PMID- 22046588
TI - Eu(II)-containing cryptates as contrast agents for ultra-high field strength
magnetic resonance imaging.
AB - The relaxivity (contrast-enhancing ability) of Eu(II)-containing cryptates was
found to be better than a clinically approved Gd(III)-based agent at 7 T. These
cryptates are among a few examples of paramagnetic substances that show an
increase in longitudinal relaxivity, r(1), at ultra-high field strength relative
to lower field strengths.
PMID- 22046589
TI - A novel bifunctional protein supramolecule for construction of carbon nanotube
titanium hybrid material.
AB - Carbon nanotube-TiO(2) hybrid materials with many nano-scale cavities were
realized using a bifunctional protein supramolecule possessing carbonaceous
material-binding peptides and Ti-binding peptides. The obtained structure was
confirmed to consist of a central nanotube, surrounding proteins, and a swathing
titanium-layer. All processes were carried out at room temperature, using an
environmentally friendly method.
PMID- 22046590
TI - Antimicrobial surface grafted thermally responsive PNIPAM-co-ALA nano-gels.
AB - Thermally responsive Poly(N-isopropylacrylamide) co-allylamine (PNIPAM-co-ALA)
nano-gels were synthesised and grafted onto non-woven polypropylene. Silver
nitrate was incorporated into the nano-gels in their expanded state and their
antimicrobial properties tested. Bacterial growth was measured before and after
the Lower Critical Solution Temperature. Below the LCST, bacteria grew, above the
LCST bacterial growth was prevented or retarded.
PMID- 22046591
TI - On the stereoselective bicyclization of aminodienes catalyzed by chelating
diamide complexes of the group 3 metals. A direct comparison of Sc(III) and
Y(III) bis(amide)s with an application to the synthesis of alkaloid 195F.
AB - Highly diastereoselective bicyclizations of aminodienes catalyzed by chelating
diamide complexes of Sc(III) and Y(III) that lead to pyrrolizidines and
indolizidines are described. This bis(annulation) procedure has been utilized in
a concise synthesis of the pyrrolizidine alkaloid 195F.
PMID- 22046592
TI - New animal models of Parkinson's disease.
AB - BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder
mainly characterized by the loss of dopaminergic neurons from the substantia
nigra pars compacta and the presence, in the affected brain regions, of protein
inclusions named Lewy Bodies. Despite the fact that numerous mutations causing
hereditary forms of Parkinson's disease have been identified in the last decade,
current transgenic animal models do not adequately reproduce cardinal features of
the human disease. Altogether, the animal models derived of human mutations
indicate that the nigrostriatal degenerative process results from the combination
of several mechanisms that implicate mitochondrial dysfunction, oxidative damage,
and protein degradation impairment. METHODS AND RESULTS: We performed a
literature search between 2008 and 2010. DISCUSSION: The absence of adequate in
vivo experimental models of Parkinson's disease has severe repercussions for
therapeutic intervention success for this incurable neurodegenerative disorder.
The present nonexhaustive review looks at invertebrate and mammalian models of
Parkinson's disease generated in the last three years.
PMID- 22046593
TI - Abstracts of the 81st Annual Meeting of the American Thyroid Association. October
26-30, 2011. Indian Wells, California, USA.
PMID- 22046594
TI - Recommended composition of influenza vaccines for use in the 2012 southern
hemisphere influenza season.
PMID- 22046596
TI - Standardization of terminology of the pandemic A(H1N1) 2009 virus.
PMID- 22046595
TI - Antigenic and genetic characteristics of zoonotic influenza viruses and
development of candidate vaccine viruses for pandemic preparedness.
PMID- 22046597
TI - Validation of elimination: maternal and neonatal tetanus in Mozambique, 2010.
PMID- 22046598
TI - Review of the 2011 winter influenza season, southern hemisphere.
PMID- 22046599
TI - [Abstracts XLI Congress of the Spanish Society of Nephrology. October 15-18,
2011. Sevilla, Spain].
PMID- 22046600
TI - Vulvar ulcers and vulvar carcinoma.
PMID- 22046601
TI - HIV partner notification is effective and feasible in sub-Saharan Africa:
opportunities for HIV treatment and prevention.
AB - BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require
HIV counseling, testing and, if necessary, evaluation for therapy. However, many
African countries do not have a standardized protocol for partner notification,
and the effectiveness of partner notification has not been evaluated in
developing countries . METHODS: Individuals with newly diagnosed HIV infection
presenting to sexually transmitted infection clinics in Lilongwe, Malawi, were
randomized to 1 of 3 methods of partner notification: passive referral, contract
referral, or provider referral. The passive referral group was responsible for
notifying their partners themselves. The contract referral group was given seven
days to notify their partners, after which a health care provider contacted
partners who had not reported for counseling and testing. In the provider
referral group, a health care provider notified partners directly. RESULTS: Two
hundred forty-five index patients named 302 sexual partners and provided locator
information for 252. Among locatable partners, 107 returned for HIV counseling
and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners
returned in the passive referral arm, 45 of 88 (51%; 95% CI: 41% to 62%) in the
contract referral arm, and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider
referral arm (P < 0.001). Among returning partners (n = 107), 67 (64%) of were
HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the
first evidence of the effectiveness of partner notification in sub-Saharan
Africa. Active partner notification was feasible, acceptable, and effective among
sexually transmitted infections clinic patients. Partner notification will
increase early referral to care and facilitate risk reduction among high-risk
uninfected partners.
PMID- 22046602
TI - A randomized crossover study to determine relative bioequivalence of tenofovir,
emtricitabine, and efavirenz (Atripla) fixed-dose combination tablet compared
with a compounded oral liquid formulation derived from the tablet.
PMID- 22046603
TI - Abstracts of the 22nd Regional Congress of the ISBT (International Society of
Blood Transfusion) Asia. Taipei, Taiwan. November 19-23, 2011.
PMID- 22046604
TI - Proposal to adjust the WHO clinical staging system.
PMID- 22046605
TI - Low uptake of hepatitis C testing and high prevalence of risk behavior among HIV
positive injection drug users in Bangkok, Thailand.
PMID- 22046610
TI - Abstracts of the 15th Meeting of the Australian and New Zealand Microcirculation
Society. November 30-December 3, 2011. Margaret River, Western Australia,
Australia.
PMID- 22046611
TI - Effects of radial compression on a novel simulated intervertebral disc-like
assembly using bone marrow-derived mesenchymal stem cell cell-sheets for annulus
fibrosus regeneration.
AB - STUDY DESIGN: The aim of this study was to develop a tissue engineering approach
in regenerating the annulus fibrosus (AF) as part of an overall strategy to
produce a tissue-engineered intervertebral disc (IVD) replacement. OBJECTIVE: To
determine whether a rehabilitative simulation regime on bone marrow-derived
mesenchymal stem cell cell-sheet is able to aid the regeneration of the AF.
SUMMARY OF BACKGROUND DATA: No previous study has used bone marrow-derived
mesenchymal stem cell cell-sheets simulated by a rehabilitative regime to
regenerate the AF. METHODS: The approach was to use bone marrow-derived stem
cells to form cell-sheets and incorporating them onto silk scaffolds to simulate
the native lamellae of the AF. The in vitro experimental model used to study the
efficacy of such a system was made up of the tissue engineering AF construct
wrapped around a silicone disc to form a simulated IVD-like assembly. The
assembly was cultured within a custom-designed bioreactor that provided a
compressive mechanical stimulation onto the silicone disc. The silicone nucleus
pulposus would bulge radially and compress the simulated AF to mimic the
physiological conditions. The simulated IVD-like assembly was compressed using a
rehabilitative regime that lasted for 4 weeks at 0.25 Hz, for 15 minutes each
day. RESULTS: With the rehabilitative regime, the cell-sheets remained viable but
showed a decrease in cell numbers and viability. Gene expression analysis showed
significant upregulation of IVD-related genes and there was an increased ratio of
collagen type II to collagen type I found within the extracellular matrix.
CONCLUSION: The results suggested that a rehabilitative regime caused extensive
remodeling to take place within the simulated IVD-like assembly, producing
extracellular matrix similar to that found in the inner AF.
PMID- 22046612
TI - Factor structure of the Neck Disability Index.
PMID- 22046613
TI - Expanded indication for recombinant human bone morphogenetic protein 2.
PMID- 22046615
TI - Abstracts of the 43rd Annual Scientific Congress of The Royal Australian and New
Zealand College of Ophthalmologists. November 19-22, 2011. Canberra, Australia.
PMID- 22046616
TI - Abstracts of Obesity 2011. October 1-5, 2011. Orlando, Florida, USA.
PMID- 22046614
TI - Risk factors for medical complication after lumbar spine surgery: a multivariate
analysis of 767 patients.
AB - STUDY DESIGN: Multivariate analysis of prospectively collected registry data.
OBJECTIVE: Using multivariate analysis to determine significant risk factors for
medical complication after lumbar spine surgery. SUMMARY OF BACKGROUND DATA:
Several studies have examined the occurrence of medical complication after spine
surgery. However, many of these studies have been done utilizing large national
databases. Although these allow for analysis of thousands of patients,
potentially influential covariates are not accounted for in these retrospective
studies. Furthermore, the accuracy of these retrospective data collection in
these databases has been called into question. METHODS: The Spine End Results
Registry (2003-2004) is a collection of prospectively collected data on all
patients who underwent spine surgery at our two institutions. Extensive
demographic and medical information were prospectively recorded as described
previously by Mirza et al. Complications were defined in detail a priori and were
prospectively recorded for at least 2 years after surgery. We analyzed risk
factors for medical complication after lumbar spine surgery using univariate and
multivariate analysis. RESULTS: We analyzed data from 767 patients who met out
inclusion criteria. The cumulative incidences of complication after lumbar spine
surgery per organ system are as follows: cardiac, 13%; pulmonary, 7%;
gastrointestinal, 6.7%; neurological, 8.2%; hematological, 17.5%; and urologic
complications, 10.3%. The occurrence of cardiac or respiratory complication after
lumbar spine surgery was significantly associated with death within 2 years
(relative risk: 6.09 and 10.9, respectively). Several significant risk factors
were identified for organ-specific complications. Among these, surgical
invasiveness appeared to be the largest risk factor for cardiac, pulmonary,
neurological, and hematological complications. CONCLUSION: Risk factors
identified in this study can be beneficial to clinicians and patients alike when
considering surgical treatment of the lumbar spine. Future analyses and models
that predict the occurrence of medical complication after lumbar spine surgery
may be of further benefit for surgical decision making.
PMID- 22046617
TI - Immunotherapy for advanced prostate cancer: a novel treatment option to improve
survival.
AB - Prostate cancer is the second leading cause of cancer death in men in the United
States. Novel immunotherapies are being investigated to improve survival in
patients with advanced disease. Sipuleucel-T (PROVENGE), the first autologous
cellular immunotherapy approved by the U. S. Food and Drug Administration,
improves survival in men with asymptomatic or minimally symptomatic metastatic
castration-resistant (hormone refractory) prostate cancer.
PMID- 22046618
TI - 2011 AHCA/NCAL National Quality Awards. Idaho gold. Recipient sees big payoff
from listening and learning.
PMID- 22046619
TI - Many mountains to climb.
AB - Medical groups of all types and sizes stand collectively at a crossroads in the
evolution of the healthcare industry in the United States at this point in time.
Faced with a welter of issues, from reimbursement concerns to mandates coming out
of federal healthcare reofrm and the American Recovery and Reinvestment/Health
Information Technology for Economic and Clinical Health (ARRA-HITECH) Act and
other legislative and regulatory developments and competing to better serve the
needs of both patients and payers and purchasers, the CEOs, CIOs and others
leading physician groups are working assiduously to find ways forward that meet
the demands of stakeholder groups while also meeting the needs of their
practicing physicians. In order to get a sense of where the leaders in the field
are at this point in time. Healthcare Informatics Eidtor-in-Chief Mark Hagland
gathered together several leaders of pioneering medical groups nationwide through
a "virtual roundtable" process late this summer, in which he interviewed
successive leaders and "shared forward" their thoughts with the others around
this "virtual roundtable". Below are excerpts from the progressive interviews.
Capsule profiles of the leaders and their organizations can be found below. Among
the many inssues facing these leaders: how to plan for the development of
accountable care organizations (ACOs), the patient-centered mdical home model,
bundled payments and other federal policy requirements; how to make progress
towards meaningful use, under the HITECH Act; how to plan for ongoing
infrastructure, interoperability, and mobility development; and how to prioritize
a variety of disparate efforts aimed at fulfilling different types of needs. No
one medical group leader has all the answers; but our panel of leaders certainly
has many important and useful perspectives to share.
PMID- 22046620
TI - CMIOs roaring ahead.
PMID- 22046621
TI - Living with stigma is still the common experience for mental health service
users.
PMID- 22046622
TI - [Tickbusters].
PMID- 22046623
TI - [The GP's diagnostic assessment considers all possibilities. Dealing competently
with uncertainty].
PMID- 22046624
TI - Effects of combination of fluticasone propionate and salmeterol xinafoate on lung
function improvement in patients with bronchiectasis.
AB - INTRODUCTION: Bronchiectasis is defined as bronchial abnormal and permanent
dilation with destructive and inflammatory changes of bronchial wall.
Bronchodilators are used to treat the disease in order to improve lung functions.
Seretide is the combination of fluticasone propionate and salmeterol xinafoate
(FLU/SAL). The effect of each has been proved in the improvement of
bronchiectasis, while their synthetic effect as FLU/SAL on bronchiectasis
improvement has not been studied yet. AIM: The aim of this study was to
investigate the effects of FLU/SAL on the lung function improvement in
bronchiectasis patients, comparing and interpreting pulmonary function tests
before and after FLU/SAL inhalation. METHODS AND MATERIALS: Twelve patients with
bronchiectasis who referred to Rasoul-e-Akram Hospital, Tehran, Iran in 2008
participated in this prospective quasi-experimental trial. The patients were
treated with 2 puffs of fluticasone 125 MUg and salmeterol 50 MUg (Seretide)
twice a day for one month. Beside recording demographic variables, the results of
pulmonary function tests (PFT) including vital capacity (VC), forced vital
capacity (FVC), forced expiratory volume in the first second (FEV1) and FEV1/FVC
ratio were recorded before and after the treatment. Data were analyzed using SPSS
v.16 and Pearson correlation and paired T-test were performed. RESULTS: Among 12
patients with bronchiectasis, there were 4 men and 8 women with the mean age of
47.58 (SD=18.32) yr. The mean increase in the ratios of VC, FVC and FEV1 to
predicted values and also patients FEV1/FVC after treatment were 15.50%
(SD=14.40), 49.83% (SD=8.19) 8.17% (SD=12.07) and 7.17% (SD=12.68), respectively.
The results of paired T-test indicated that VC (P=0.008) and FEV1(P=0.039) have
increased significantly after treatment. CONCLUSION: This study is one of the
first studies investigating the FLU/SAL effect on bronchiectasis. Results of this
study have indicated that using FLU/SAL has a significant effect on the
improvement of lung function parameters in these patients, while the attention
was been focused on antibiotic therapy or other bronchodilators.
PMID- 22046625
TI - Melanoma sentinel lymph node biopsy: analysis of cases operated on from 1999 to
2008 in The University Hospital Dubrava, Zagreb, Croatia.
AB - TITLE: Melanoma Sentinel Lymph Node Biopsy: analysis of cases operated on from
1999-2008 in the University Hospital Dubrava, Zagreb, Croatia. AIM: To determine
how well tumor thickness, ulceration, location and patient age and sex predict a
positive sentinel lymph node in the analyzed population. PATIENTS AND METHODS:
321 patients were included in the study. 53% (169) were male and 47% (152) were
females. 291 underwent sentinel lymph node biopsy. The median age was 56 years
(age range 20-89). Sentinel lymph node biopsy was performed by lymphoscintigraphy
using technetium-99m (99mTc)-labeled sulfur colloid and vital dye. RESULTS:
Melanomas were similarly distributed on the trunk (154, 48%) and the extremities
(145, 45%), a small number was located on the head and neck (12, 4%) and for 10
(3%) there was no record of the location. Positive lymph nodes were detected in
76 (26%) out of 291 patients who underwent sentinel lymph node biopsy.
Micrometastases were found in 50 basins (60%), macrometastases were found in 15
basin (18%), one basin contained a metastasis that was spreading beyond the
capsule (1%) and in the remaining 18 (21%) positive basins in the identified
sentinel lymph nodes contained only isolated tumor cells. The average melanoma
thickness of 3.41mm for sentinel lymph node biopsy positive melanomas was
significantly greater than 2.47mm for negative melanomas (p=0.006).
Proportionally more positive sentinel lymph nodes were found with increasing
tumor thickness, (p=0.061). Ulceration was found to be a good predictor of
positive sentinel lymph nodes (p<0.001). When comparing upper and lower
extremities, sentinel lymph nodes were significantly more positive when the
primary melanoma was on the legs (p=0.04). An ulcerated primary melanoma on the
extremities was found more likely to have a positive sentinel lymph node
(p=0.04). A significantly higher proportion of those older than 50 years old had
positive lymph nodes (p<0.001). CONCLUSION: Tumor thickness, ulceration, location
(upper vs. lower extremities, on the extremities with ulceration) as well as the
age of the patient (>50) were found to be predictors of sentinel lymph node
positivity. Clinically negative patients with any of these factors should be
considered candidates for sentinel lymph node positivity.
PMID- 22046626
TI - Evaluation of the simvastatin effects in the treatment of pulmonary hypertension
(PH).
AB - BACKGROUND: Pulmonary hypertension (PH) is a rare but life-threatening disease
characterized by significant increases in pulmonary arterial pressure (PAP) and
right ventricular hypertrophy (RVH), therefore early diagnosis and proper
treatment of PH is very important. Statins confer cardiovascular benefits beyond
the reduction of serum cholesterol through antiproliferative and antiinflammatory
mechanisms and induction of endothelial nitric oxide expression. In
pneumonectomized rats injected with monocrotaline, simvastatin reversed
established pulmonary hypertension and conferred a 100% survival advantage.
OBJECTIVE: The aim of this study was to evaluate the potential effect of
simvastatin treatment in patients with pulmonary hypertension (PH). PATIENTS AND
METHODS: In this prospective before-after pilot trial, 19 patients with primary
and secondary causes of PH referred to Khorrami Hospital in Qom, Iran were
recruited. Patients were treated with simvastatin, beginning at 20 mg/daily for 2
months, then increasing to 40 mg/daily for another 4 months. Echocardiographic
Doppler estimates of systolic pulmonary artery pressures (SPAP) were measured for
each patient before prescribing simvastatin and at the end of treatment. Also
demographic data, history of smoking and heart functional class (NYHA) before and
after treatment were recorded. RESULTS: Out of 19 patients with PH, fifteen were
males (78.95%) and four were females (21.1%) with the mean age of 66 (SD=15.28)
yr, range between 18 to 83 years. The commonest cause of PH was chronic
obstructive pulmonary disease (COPD) in 15 patients (78.9%). Simvastatin
significantly ameliorated PH from 74.79 (SD=23.52) mmHg to 67.21 (SD=20.55) mmHg
(P<0.001). Whereas, heart functional class changes were not statistically
significant (P=0.157). CONCLUSION: In this study, we demonstrated that
simvastatin treatment decreased SPAP in patients with PH. As the pathogenesis of
PH involves inappropriate proliferation and constriction of vascular smooth
muscle cells, and deficiencies of endogenous vasodilators such as prostacyclin
and endothelial-derived nitric oxide, the antiproliferative, antiinflammatory and
antithrombogenic effect of simvastatin seems to be useful. This study has led
physicians to believe that simvastatin may be beneficial for the treatment of PH.
PMID- 22046627
TI - Treatment of symptomatic coronary artery disease with stent implantation.
AB - BACKGROUND: Percutaneous coronary intervention (PCI) with stent implantation is
the therapy of choice for treatment of decreased blood flow through the coronary
arteries. AIM: We evaluated the efficacy of the bare metal stent (BMS) for
treatment of symptomatic coronary artery disease and compared BMS with the drug
eluting stent (DES) to find out which one is better in the prevention of major
adverse cardiac events (MACE) six months after stent implantation. MATERIALS AND
METHODS: Our retrospective analysis included 387 consecutive patients with BMS
implantation and 74 consecutive patients with DES implantation. Efficacy of BMS
was evaluated by residual in-stent stenosis after the procedure. According to the
Taxus II-Trial definition, MACE include cardiac death, acute myocardial
infarction (AMI) and target vessel revascularization; the latter includes PCI
with stent implantation or coronary artery bypass graft on previously
revascularized vessel. RESULTS: In BMS group mean pre-procedure stenosis diameter
was 81.9 +/- 12.8% and mean post-procedure stenosis was 4.8% +/- 12.5%. The
residual in-stent stenosis was significantly higher in patients with longer
lesions (p<0.05). Hypertension was the most frequent risk factor in both groups
and AMI the commonest indication for stent implantation in the group with BMS,
while stable and unstable angina pectoris in the group with DES, respectively.
During the first six months after the implantation of DES, the incidence of MACE
was significantly lower (p<0.05) compared to BMS. The most frequent subgroup of
MACE present in the group with BMS was cardiac death, and in the group with DES
it was repeated PCI with stent implantation. CONCLUSIONS: BMS provides and
efficacious choice of treatment for patients with symptomatic coronary artery
disease. Patients with longer lesions have higher residual in-stent stenosis
after BMS implantation. Implantation of DES is more successful in preventing MACE
in comparison with the implantation of BMS.
PMID- 22046628
TI - Bibliometric analysis of primary care research, childhood obesity, the importance
of understanding small area data and diabetes.
PMID- 22046629
TI - Retraction. Detection of ubiquityl-calmodulin conjugates with a novel high
molecular weight ubiquitylprotein-isopeptidase in rabbit tissues.
PMID- 22046630
TI - The discovery of histone deacetylase.
PMID- 22046631
TI - Historical development of pediatric pharmacology.
PMID- 22046632
TI - Medicare program; final waivers in connection with the Shared Savings Program.
Interim final rule with comment period.
AB - This interim final rule with comment period establishes waivers of the
application of the Physician Self-Referral Law, the Federal anti-kickback
statute, and certain civil monetary penalties (CMP) law provisions to specified
arrangements involving accountable care organizations (ACOs) under section 1899
of the Social Security Act (the Act) (the Shared Savings Program), including ACOs
participating in the Advance Payment Initiative. Section 1899(f) of the Act, as
added by the Affordable Care Act, authorizes the Secretary to waive certain fraud
and abuse laws as necessary to carry out the provisions of section 1899 of the
Act.
PMID- 22046633
TI - Medicare program; Medicare Shared Savings Program: Accountable Care
Organizations. Final rule.
AB - This final rule implements section 3022 of the Affordable Care Act which contains
provisions relating to Medicare payments to providers of services and suppliers
participating in Accountable Care Organizations (ACOs) under the Medicare Shared
Savings Program. Under these provisions, providers of services and suppliers can
continue to receive traditional Medicare fee-for-service (FFS) payments under
Parts A and B, and be eligible for additional payments if they meet specified
quality and savings requirements.
PMID- 22046634
TI - Spinal cord injuries.
PMID- 22046635
TI - Arterial vascularization of the spinal cord. Recent studies of the anastomotic
substitution pathways.
AB - This study of the arterial blood of the spinal cord indicates that, of the 62
radicular branches (rami radiculares), at the most seven or eight truly
participate in the vascularization of the spinal cord. The authors have observed
that the situation and distribution of these branches enable the distinction of
three large arterial areas: cervicothoracic, midthoracic, and thoracolumbar. The
fixed nature of the intramedullary arterial distribution contrasts with the
variability of the afferent arterial supplies. No demarcation permits separation
of the vascularization of the spinal cord into anterior and posterior parts. The
anastomotic systems situated on the arterial pathways are potentially valuable,
but their functioning is problematical. The anterior spinal artery is not
continuous, for in the midthoracic region there exists a critical narrow zone.
The perimedullary anastomotic system appears insufficient while intramedullary
anastomoses are without functional value.
PMID- 22046636
TI - The microvasculature in transitory traumatic paraplegia. An electron microscopic
study in the monkey.
AB - Fine structural alterations in the microvasculature, primarily of the gray
matter, occur as one aspect of experimental spinal cord contusion. A force of 300
gm-cm, shown by the authors to produce a transitory paraplegia, was applied to
the T-10 level of exposed primate spinal cord. At 5 min post-contusion, the
muscular venules of the central gray matter were distended with erythrocytes.
Erythrocytes were seen within the perivascular spaces of the post-capillary
venules and muscular venules at 15 and 30 min post-contusion, and there was
hemorrhage into the gray matter at 1 hour post-contusion. The appearance of
erythrocytes within the perivenular spaces was apparently due to small ruptures
in the walls of the muscular venules, which were first demonstrated by electron
microscopy 15 min after contusion. Alterations in capillary and post-capillary
venule endothelium of both gray and white matter were present at 4 hours post
contusion and consisted of vacuolation and endothelial swelling. In conclusion,
following experimental contusion of the spinal cord sufficient to cause a
transitory paraplegia, the principal changes were early perivascular and
parenchymal hemorrhages followed by later evidence of ischemic endothelial injury
in the microvasculature.
PMID- 22046637
TI - Histopathology of transitory traumatic paraplegia in the monkey.
AB - The microscopic appearance of the primate spinal cord within a 4-hour interval
following the delivery of a direct force sufficient to produce a transitory
paraplegia was investigated by light microscopy. The resulting hemorrhagic lesion
involved primarily the central gray matter and was attributed to the direct
effect of the trauma on the vessels in the gray matter with a consequent
impairment of blood supply to the injured area. Chromatolysis, vacuolation, and
alterations in cytoplasmic density and stainability were observed within the
neurons. The edematous changes in the white matter, which were more marked in the
internal layers relative to the external layers, appeared minimal and explain in
part why the paraplegia was transient.
PMID- 22046638
TI - Microangiographic study of experimental spinal cord injuries.
AB - The pathology of spinal cord injury has been studied in 34 rabbits and 5 dogs
with attention focused on the condition of the microvasculature during the
evolution of neuronal and axonal degeneration and necrosis. The animals were
killed and perfused arterially with colloidal barium from 10 min to 14 days after
a controlled spinal injury. Microradiographs of the injured tissues were obtained
and compared with corresponding histological sections. Microangiography at 7 to
14 days defines two zones in the injured spinal cord. Zone 1 is located in the
posterocentral part of the cord. Capillaries in this region progressively lose
their ability to conduct blood and perfusate over the first 4 hours. Degenerative
changes in neurons are visible by 1 hour after injury. Necrosis of all elements
including capillaries ensues. Zone 2 surrounds Zone 1. Microvascular patterns are
normal in Zone 2 although neuronal and axonal degeneration is severe.
Pericapillary hemorrhages which occur as early as 10 min after injury in Zone 1
and become progressively larger over the first 4 hours seldom are seen in Zone 2.
The evidence indicates that at all times in the pathogenesis of spinal cord
injury the microvasculature in Zone 2 is capable of perfusion. Degeneration of
neural structures either precedes microvascular breakdown (Zone 1) or occurs in
the absence of microvascular disruption (Zone 2). Recovery of damaged neurons and
axons depends upon a preserved microcirculation.
PMID- 22046639
TI - Denervation hyperpathia: a convulsive syndrome of the spinal cord responsive to
carbamazepine therapy.
AB - Two cases of denervation hyperpathia that responded well to treatment with
carbamazepine are presented. A theoretical relation of this disorder to
trigeminal neuralgia and focal seizures is emphasized in the light of
experimental data and clinical characteristics.
PMID- 22046640
TI - Surgical treatment of multiple aneurysms and of incidentally-discovered
unruptured aneurysms.
AB - Review of a series of 460 patients with spontaneous intracranial hemorrhage
showed that 241 had demonstrable aneurysms and 38 had multiple aneurysms. The
importance of demonstrating the entire circulation following ligation of one
aneurysm is emphasized. Treatment of the 38 patients with multiple aneurysms is
described. Ligation of unruptured aneurysms that are incidentally discovered is
advocated in patients who are Grade 1 on the Botterell scale and who are well
informed as to the risks.
PMID- 22046641
TI - Angiographic demonstration of brain injury without significant mass lesion.
AB - Evidence of brain damage was demonstrated in two patients without significant
mass lesions by the presence of early venous filling and abnormal contrast
staining. The vascular changes were most prominent on subtraction films. It is
likely that these angiograms demonstrated the "luxury perfusion" phenomenon
described previously in areas of damaged brain.
PMID- 22046642
TI - The deposition of Hg203-chlormerodrin in experimental brain tumors.
AB - The deposition of Hg203-chlormerodrin was studied in intracranial tumors in mice
induced by implantation of 20-methyl cholanthrene by tissue assay, as well as
light microscopic and electron microscopic autoradiography. The investigations
were carried out in astrocytomas, glioblastomas, and meningeal tumors. The
chlormerodrin content of the tumors exceeded that of normal brain with a
significant tumor/brain ratio ranging from 5.8 to 22.5. It was found that the
chlormerodrin molecule becomes rapidly incorporated in the tumor cells, with a
preference for that portion of the cytoplasm associated with the vacuolar system.
PMID- 22046643
TI - Ventriculoatrial shunt in tuberculous meningitis with hydrocephalus.
AB - Raised intracranial tension affects the course of tuberculous meningitis
adversely. The development of hydrocephalus may account for the raised
intracranial pressure. Insertion of a ventriculoatrial shunt significantly alters
the course of the disease. The results in seven cases have been detailed and
discussed. The levels of consciousness improved, hemiplegia and aphasia
practically cleared up, and vision returned even in children who were blind for 4
to 6 weeks. Operation could be performed even in an active stage of the disease
without much fear of miliary dissemination.
PMID- 22046644
TI - Pre- and postoperative electromyographic evaluations in the carpal tunnel
syndrome.
AB - Twenty-five cases of carpal tunnel syndrome in 20 patients were evaluated
preoperatively and postoperatively by electromyography. Clinical improvement
resulted in all cases following decompression of the median nerve, and only in a
few instances did mild symptoms persist. Distal motor conduction time im proved
postoperatively in 24 cases studied, 19 of which returned to normal range. Most
of the obvious improvement occurred within the first 3 months and further
improvement could be observed as late as 36 months. Although no definite
correlation could be established between the preoperative severity of the carpal
tunnel syndrome and the postoperative clinical and electrical im provement, there
was a definite evidence of better recovery in the younger age group. There was a
greater range of improvement and a return closer to normal postoperatively in
cases with severe preoperative distal latency. All cases ex amined after 24
months had reached normal values.
PMID- 22046645
TI - Simple cysts of the cerebellum.
AB - Four cases of simple cyst of the cerebellum treated at Stanford University
Medical Center are presented. Review of the literature and past experience at
Stanford suggest that they are uncommon. They seem to occur most often in middle
age, presenting the signs and symptoms of an expanding cerebellar mass, and
appear to be adequately treated by unroofing and draining the cyst cavity. It is
suggested that these cysts do not have a congenital origin but rather represent a
degenerated form of cerebellar astrocytoma.
PMID- 22046648
TI - Lipoma of the spinal cord. Case report.
AB - A case of intradural spinal lipoma has been reported. Its pathological and
clinical features are compared with those of 129 other cases collected from the
literature.
PMID- 22046646
TI - Transfemoral vertebral angiography as a cause of an anterior spinal artery
syndrome. Case report.
AB - A case with signs of a lower cervical anterior spinal artery syndrome incident to
vertebral angiography by the transfemoral approach is described. The literature
is reviewed and a probable pathogenesis of angiography-related spinal cord injury
is discussed.
PMID- 22046647
TI - Osteoid osteoma of the cervical spine. Case report.
AB - A case of osteoid osteoma involving the cervical vertebral pedicle is presented
which reemphasizes the importance of complete removal of the nidus and the
dramatic relief of symptoms following excision.
PMID- 22046649
TI - Dysphagia secondary to anterior cervical osteophytes. Report of two cases.
AB - Two cases of dysphagia secondary to anterior cervical osteophytes were
successfully treated at the University of Oregon Medical School by surgical
excision of the osteophytes. In both cases the cervical osteophytes caused
mechanical obstruction to deglutition by esophageal compression. Postoperative x
ray examination confirmed relief of obstruction. Related cases, clinical
features, diagnostic steps, and possible mechanisms are discussed.
PMID- 22046650
TI - Survival following gunshot wound of the pons: neuroanatomic considerations. Case
report.
AB - The successful treatment of a civilian gunshot wound of the vermis and pons is
described. A large missile fragment was removed from a depth of 2 cm within the
pons at the level of the facial colliculus. Despite initial coma and subsequent
irregular respiration with sleep apnea, the patient survived. Neurological,
radiographic, and operative findings are correlated with the anatomy of the pons.
PMID- 22046651
TI - Retrograde migration of the venous catheter as a complication of ventriculoatrial
shunts in adults. Case report.
AB - The retrograde cephalad migration of the flexible venous catheter into a large
internal jugular vein is described in two cases of adult "normal" pressure
hydrocephalus treated with Holter ventriculoatrial shunts. The successful
correction of this problem by replacement of the standard type "C" catheter with
a slightly more rigid catheter and internal jugular vein ligation is described.
PMID- 22046652
TI - An internal shunt for use in the reconstruction of dural venous sinuses.
Technical note.
AB - A technique is described for construction and use of an internal shunt which
provides hemostasis and permits blood flow through the injured sinus during the
period of repair. An illustrative case is presented.
PMID- 22046653
TI - A soluble internal splint for experimental vascular anastomosis. Technical note.
AB - The authors have developed, in dogs, a nonsuture vascular anastomosis utilizing
plastic adhesive and a water-soluble spindle tube composed of 80% saccharose, 16%
glucose, and 4% dextrin. The patency rate of end-to-end arterial anastomosis was
70% in arteries with an external diameter of 2.5 to 4.0 mm. The device is easily
applied, saves time, and does not require any special instruments.
PMID- 22046654
TI - Percutaneous cordotomy.
AB - The essentials for performing a safe and satisfactory percutaneous cordotomy are:
(1) a suitable type of pain in a patient without respiratory hazard, (2) a very
fine electrode, (3) contrast visualization of the dentate ligament, (4)
electrical stimulation before lesion making, (5) slow increase in strength of the
lesion-making current, (6) careful motor as well as sensory testing between
lesions, (7) a willingness to desist in the face of difficulties, and (8) an
awareness of the possibility of respiratory problems in the postoperative period.
PMID- 22046655
TI - The International Symposium on Head Injuries.
PMID- 22046656
TI - [Extended medical education--at any cost?].
PMID- 22046657
TI - [EU questions Swedish internship which is now under investigation].
PMID- 22046658
TI - [Gender and myocardial infarction. Treatment measures not the same as results].
PMID- 22046659
TI - [Alcohol during early pregnancy damages human stem cells. Important that pregnant
women receive information about new knowledge from an experimental study].
PMID- 22046660
TI - [Preoperative withdrawal of drugs that affect hemostasis. Evidence-based
recommendation].
PMID- 22046661
TI - [Neonatal and maternal risks with IVF are small and decreasing].
PMID- 22046662
TI - [Difficult to treat lithium-associated hyperparathyroidism with surgery. Evidence
for optimal therapy is still missing].
PMID- 22046663
TI - [A pediatric lack of knowledge. FPIES--a non-IGF-mediated food allergy with
dramatic symptoms].
PMID- 22046664
TI - [Clinical nutrition should be reintroduced as medical specialty!].
PMID- 22046665
TI - [Mobile phones and brain tumours--a scientific controversy].
PMID- 22046667
TI - Few nurses make NHS top jobs list.
PMID- 22046666
TI - [Beyond the physician's knowledge map. Important to see the patient as a human
being--not the other way round].
PMID- 22046668
TI - "Don't experiment with skill mix without rigorous assessment".
PMID- 22046669
TI - "We don't need time travel to know that PFI was unwise".
PMID- 22046670
TI - Attitudes towards Gypsy Travellers.
AB - Gypsy Travellers often experience wide-ranging inequalities, associated with poor
access to health services and education, discrimination, and health
professionals' lack of understanding of the cultural identity and health needs of
their community. This article explores nurses' attitudes to Gypsy Travellers, and
discusses how overcoming bias and negativity can help address the health needs of
this community.
PMID- 22046671
TI - Defibrillation 2: Using defibrillators in hospital.
AB - Patients who have a cardiac arrest in hospital should, if it is indicated, be
defibrillated as quickly as possible--ideally within three minutes. Most hospital
wards and other clinical areas have access to defibrillators with both advisory
(semi-automated) and manual modes. The former enables first responders, including
nurses without ECG interpretation skills, to defibrillate the patient while
awaiting the arrival of the cardiac arrest team who can then select and use the
manual mode. Most hospital nurses will be trained in advisory defibrillation,
while a few will be trained in manual defibrillation. This article provides an
overview of defibrillation in hospital, and looks at both advisory and manual
defibrillation.
PMID- 22046672
TI - Implementing nurse-led discharge.
AB - Many hospitals have for years tried to introduce nurse-led discharge but the
evidence suggests this has not been entirely successful. Projects have failed due
to lack of engagement from staff, failure to monitor outcomes and lack of
sustainability. This article describes the early stages of the introduction of
nurse/midwife-led discharge at the Heart of England Foundation Trust, which
attempted to address these issues.
PMID- 22046673
TI - Improving the hydration of hospital patients.
AB - Dehydration occurs when the body loses fluids at a greater rate than it takes in.
For some patients, achieving a fluid balance is difficult without assistance and
they rely on interventions by health professionals. In 2009, a fluid balance
audit was carried out in an acute hospital. The aim was to identify whether
clinical practice could be improved, and if health professionals could assist
their patients' hydration during their admission by using a hands-free drinks
system.
PMID- 22046674
TI - Local winner.
PMID- 22046675
TI - Values are vital to overall success.
PMID- 22046676
TI - [Can we avoid going in the wrong direction?].
PMID- 22046677
TI - [Facial palsy: update for the practitioner].
AB - The clinical significance of facial palsy hinges on its psychosocial
consequences. While its causes are very numerous, several infections account for
a majority of cases: Lyme disease, geniculate zoster (Ramsay Hunt syndrome),
while the role of HSV-1 in essential (Bell's) palsy remains controversial.
Essentials of facial palsy management are discussed, including the importance of
the functional grading of palsy, the complexity of Lyme disease serological
diagnosis, and its treatment using doxycycline, antiviral and steroids treatment
of geniculate zoster, while regarding essential facial palsy, only steroids, but
not antiviral have been shown to improve functional recovery.
PMID- 22046678
TI - [Advantage of facial rehabilitation after facial palsy].
AB - Visible and immediate trauma, facial palsy (FP) covers functional but also
psychological damage and it is essential to evaluate before a comprehensive
therapeutic care tailored. Few patients, however, are emerging with a
prescription for rehabilitation after a consultation. Why? This rehabilitation is
it ignored? Is it absolutely necessary? It is evident in the extension of medical
care to minimize the effects. Yet the foundation of rehabilitation is sadly
little known and often poorly enforced. In addition to its specificity, this
therapy preceded by a report called "pretreatments offers a prognosis for
recovery to patient" regardless of the origin and degree of involvement of the
PF.
PMID- 22046679
TI - [Surgical facial reanimation after persisting facial paralysis].
AB - Facial reanimation following persistent facial paralysis can be managed with
surgical procedures of varying complexity. The choice of the technique is mainly
determined by the cause of facial paralysis, the age and desires of the patient.
The techniques most commonly used are the nerve grafts (VII-VII, XII-VII, cross
facial graft), dynamic muscle transfers (temporal myoplasty, free muscle
transfert) and static suspensions. An intensive rehabilitation through specific
exercises after all procedures is essential to archieve good results.
PMID- 22046680
TI - [HPV associated head and neck cancers].
AB - The incidence of oropharyngeal squamous cell carcinoma is rising and this
increase is linked to sexual behaviors. Viral and epidemiological studies have
linked tonsillar and base of tongue carcinoma with a human papilloma virus (HPV)
infection. The patients involved are usually younger and do not exhibit other
risk factors such as smoking and alcohol abuse. HPV positive squamous cell
carcinoma are associated with a better prognosis than other head and neck
carcinoma. Differences in the carcinogenesis mechanisms open options for
different and specific oncologic treatments and the potential for prevention of
these HPV-related carcinoma by vaccination.
PMID- 22046681
TI - [Tracheal replacement grafts: current options].
AB - A critical review of publications on tracheal reconstruction is presented. The
extent of the resection defect in terms of horizontal circumference or
longitudinal extension determines the difficulty of the reconstruction. To allow
a valid comparison, a classification of tracheal defects is proposed. The
reconstruction materials can be subdivided into synthetic grafts, autografts,
allografts, and bioengineering constructs. Reconstruction of tracheal defects
greater than half of the tracheal length was not possible until recently.
Numerous publications on animal experimental techniques, and rare human case
reports show few successful outcomes. During the last five years, new
reconstructive options have emerged: autograft of composite flaps mimicking
tracheal architecture and bioengineered tracheal constructs.
PMID- 22046682
TI - [Carotidynia and Eagle syndrome: two neck pain syndromes to be rediscovered].
AB - Two classical syndromes of upper cervical pain in the carotid region are
discussed: carotidynia and Eagle syndrome. In both cases, after an initial period
of enthusiasm, poorly defined diagnostic criteria led to frequent wrong diagnosis
and poor treatment responses. This led to doubts about the existence of these
syndromes. New radiologic diagnostic criteria have emerged and should allow for a
more precise diagnosis. With the correct diagnosis, medical and surgical
treatments should be better tailored and more efficient.
PMID- 22046683
TI - [Wonder and indignation, engine of life, youthfulness of heart].
PMID- 22046684
TI - [Alzheimer disease, an exemplary problem].
PMID- 22046685
TI - [A dizzying end of the week].
PMID- 22046686
TI - [The death penalty: the importance of finding a vein].
PMID- 22046687
TI - [Homosexuality and blood donation (4)].
PMID- 22046688
TI - [Walking around the hospital].
PMID- 22046689
TI - Talon cusps: conservative management.
AB - Talons cusp is an uncommon developmental dental anomaly characterized by presence
of an accessory cusp like structure projecting from tooth neck towards incisal
edge. This anomaly commonly affects permanent dentition than primary dentition.
This article describes early diagnosis and management of two patients with talons
cusp. Conservative treatment by selective grinding, followed by fluoride varnish
application was done. The patients were followed up for one year without any
complications. This indicates conservative means of management to be the most
desirable way of managing such anomalies.
PMID- 22046690
TI - Intra-coronal bleaching in young permanent and primary tooth with biologic
perspectives.
AB - The odd attracts society in odd manner, as is the case when a patient with
discolored tooth smiles. Because of that, pediatric patients have psychological
impact. Trauma and pulpal necrosis are the most common causes for discoloration
of teeth. If tooth is intact, intra-coronal bleaching is the most conservative
and noninvasive treatment modality provided, it is done cautiously. This article
intends to present two case-reports of successful intra-coronal bleaching using
milder (sodium perborate) and tissue-friendly bleaching agent with walking
bleach.
PMID- 22046691
TI - Dentistry for Mexicans with special needs: a commentary.
AB - There are more than 2 million residents with disabilities in Mexico. Despite
national legislation to assure individuals with disabilities needed services,
including education and employment, social inclusion of these individuals is
difficult since societal views exclude them from functioning as members of a
community. While there are no national studies of the dental needs of individuals
with disabilities in Mexico, reports of the general population indicate limited
use of dental services and the need for increased restorative services. Examples
of dental education accreditation standards in other countries are used as models
for the improvement in the preparation of dental students to provide services for
individual with special needs.
PMID- 22046692
TI - Comparison between rotary and manual techniques on duration of instrumentation
and obturation times in primary teeth.
AB - OBJECTIVE: The aim of this study was to compare the duration of instrumentation
and obturation times and quality of root canal filling between rotary and manual
instrumentation techniques in primary teeth. STUDY DESIGN: A randomized,
controlled clinical trial was performed that included deciduous teeth with pulp
necrotic. Forty necrotic teeth were included; 20 were instrumented with a rotary
technique (experimental group) and 20 with a manual technique (control group).
The time taken for instrumentation and for obturation were recorded in minutes,
and the quality of the root canal filling was recorded as optimal, under-filled,
or overfilled. RESULTS: The use of the rotary technique diminished the time of
instrumentation to 63% and time of obturation to 68%, and it improved the quality
of the root canalfilling. CONCLUSION: The use of rotary instruments in the
pulpectomy of primary molars represents a promising technique; the time is
significantly reduced.
PMID- 22046693
TI - Endoflas, zinc oxide eugenol and metapex as root canal filling materials in
primary molars--a comparative clinical study.
AB - Several materials have been used to fill root canals of primary teeth.
Traditionally, zinc oxide eugenol was used for the purpose, until the
introduction of calcium hydroxide and iodoform based materials. Another root
canal filling material that contains zinc oxide eugenol, calcium hydroxide and
iodoform is commercially available as Endoflas. The aim of the study was to
evaluate and compare the efficacy of Endoflas, zinc oxide eugenol and Metapex as
root canal filling materials. METHOD: A total of forty-five primary molars from
children aged 5-9 years were selected for a one stage pulpectomy procedure. Teeth
were randomly divided into three groups of fifteen teeth each based on the type
of root canal filling material used. All the molars were evaluated clinically and
radiographically at regular intervals of 3, 6, 12 and 18 months. The observations
were tabulated and statistically analyzed. RESULTS: Endoflas and zinc oxide
eugenol showed 93.3% success, whereas a higher percentage of success was observed
with Metapex (100%). Overfilling and voids were more commonly seen in teeth
filled with Metapex. CONCLUSION: There was no significant difference between the
three root canal filling materials.
PMID- 22046694
TI - Assessment of pediatricians dental knowledge, attitude and behavior in Jeddah,
Saudi Arabia.
AB - Early assessment of the oral health status of children has the potential to
reduce or even eliminate oral diseases. Parents rarely take their children to
dentist early enough to control dental diseases. However, parents contact
pediatricians several times even before the child is born and during the child's
early life. Accordingly, pediatricians are considered a perfect and reliable
source for oral health control and prevention. AIM: To measure the dental
knowledge, attitude and behavior (KAB) of pediatricians in the City of Jeddah
regarding oral health status and methods for prevention of dental diseases in
children. MATERIALS AND METHOD: Questionnaires consisting of 40 demographic and
KAB's questions were distributed to all pediatricians in Jeddah city (605
pediatricians). The KABs' questions consisted of general dental knowledge,
preventive dental measures, timing for referral, diet counseling, parafunctional
habits and handling of traumatized teeth. A score was given for each question.
Percentages of total scores of KABs were compared. RESULTS: The response rate of
pediatricians in Jeddah city (363) was 60%. Their mean age was 39.57 years.
Pediatricians' KABs were found to be unsatisfactory. The most important
observation was that the concept of oral health prevention was deficient.
Pediatricians' awareness of fissure sealants, fluoride, dietary counseling, time
of first dental visits and thumb sucking were quite limited Pediatricians'
knowledge was significantly lower than their attitude and behavior's scores.
CONCLUSION: In general, pediatricians' knowledge, attitudes and behavior
regarding oral health were not satisfactory.
PMID- 22046695
TI - Evaluation of primary tooth enamel surface morphology and microhardness after
Nd:YAG laser irradiation and APF gel treatment--an in vitro study.
AB - OBJECTIVE: Laser irradiation and fluoride has been used as a preventive tool to
combat dental caries in permanent teeth, but little has been done for primary
teeth which are more prone to caries. The purpose of this study was to evaluate
microhardness alterations in the primary tooth enamel after Nd-YAG laser
irradiation alone and combined with topical fluoride treatment either before or
after Nd-YAG laser irradiation. METHOD: Ten primary molars were sectioned and
assigned randomly to: control group, Nd-YAG laser irradiation, Nd-YAG lasing
before APF and APF followed by Nd-YAG lasing. The groups were evaluated for
microhardness. Surface morphological changes were observed using SEM. RESULTS:
Statistical comparisons were performed. The control group's SEM showed a
relatively smooth enamel surface and lasing group had fine cracks and porosities.
In the lasing + fluoride group a homogenous confluent surface was seen. In the
fluoride + lasing group an irregular contour with marked crack propagation was
noted. There was a significant increase in the microhardness of the treatment
groups. CONCLUSION: Nd-YAG laser irradiation and combined APF treatment of the
primary tooth enamel gave morphologically hardened enamel surface which can be a
protective barrier against a cariogenic attack.
PMID- 22046696
TI - Pulp calcification in traumatized primary teeth: prevalence and associated
factors.
AB - AIM: To establish the prevalence of pulp calcifications in 946 patients at the
Research and Clinical Center of Dental Trauma in Primary Teeth. STUDY DESIGN: The
clinical and radiographic records of l675 traumatized primary teeth were
evaluated. Statistical analysis was performed using chi-square and univariate
logistic regression. RESULTS: 197 (20.8%) patients showed pulp calcification
(PC). A total of 250 (14.9%) calcified teeth were observed In most teeth, PC
appeared within the first 12 months following trauma. PC prevalence was higher in
cases of repeated trauma (29.6%) than in single trauma (16.4%), p < 0.05, with a
2.14 chance of showing pulp calcification when a child suffered recurrent trauma.
Most teeth showing calcified pulp, suffered trauma to the supportive tissue
(67.4%), being statistically significant in relation to the trauma to dental
tissue (p < 0.05). CONCLUSION: PC is a sequelae in cases of trauma to the primary
dentition; teeth that suffered recurrent traumatic injuries show higher risk of
presenting.
PMID- 22046697
TI - Caries protective agents in human milk and bovine milk: an in vitro study.
AB - OBJECTIVES: To estimate Calcium and Phosphorus withdrawal from hydroxyapatite in
the presence of bovine milk and human milk from which the following protective
fractions namely Casein, Whey protein, Lactose and Milk fat have been
individually removed and to compare the above protective fractions in human and
bovine milk. METHOD: Human milk obtained from lactating mothers in the labor ward
of Kshema hospital was subjected to immediate analysis. Bovine milk was obtained
from a local dairy. Equal quantities of human milk and bovine milk (1 ml) were
separately subjected to the systematic removal of the four milk fractions. As
each fraction was removed, the remaining milk samples were subjected to testing.
Powdered hydroxyapatite from human dental enamel was subjected to
demineralization with the addition of the milk sample under test for 20 minutes.
This mixture was then centrifuged. Aliquots of the supernatant were taken for
calcium and Phosphorus analysis using photospectrometry. Ten demineralization
tests were similarly carried out for every milk fraction for both human and
bovine milk separately. Equal samples of whole bovine milk and whole human milk
were also subjected to similar testing. RESULTS: The calcium and phosphorus
dissolution values were higher when the individual fractions were eliminated from
both human milk/enamel samples and bovine milk/enamel samples as compared to the
values obtained from whole human milk/whole bovine milk/enamel samples. Further
higher calcium and phosphorus dissolution values were observed when the fractions
were individually and separately removed from the whole human milk/enamel samples
as compared to the corresponding values obtained when these fractions were
removed from bovine milk/enamel samples. CONCLUSION: The evaluated milk fraction
in bovine milk namely casein, whey protein, lactose and milk fat were
individually more caries protective when compared to the corresponding fractions
in human milk.
PMID- 22046698
TI - Oral rehydration salt-liquid as an alternative storage medium--a preliminary
study.
AB - OBJECTIVE: To assess the efficacy of Oral Rehydration Salt-Liquid (ORS-L) in the
maintenance of the viability of Periodontal ligament cells (PDL). MATERIALS AND
METHOD: Twenty freshly extracted teeth were used for this study. They were then
randomly divided into 3 groups: Positive control group--5 teeth which were
immediately subjected to collagenase assay, without immersing in ORS-L; Negative
control group--5 teeth with an extra oral dry time of 24 hours, followed by
subjecting to collagense assay without immersing in ORS-L and Test group (ORS-L)-
10 teeth with an extra oral dry period of 30 minutes, followed by immersion in
ORS-L for a period of 45 minutes and then subjected to collagenase assay. The
mean number of viable PDL cells were counted on a hemocytometer under 20X
magnification. RESULTS: The mean number of viable PDL cells was highest in the
positive control group. In comparison to the negative control group, the test
group showed a higher number of viable PDL cells. CONCLUSION: The study found
that ORS-L was an effective solution in maintaining the viability of PDL cells.
PMID- 22046699
TI - Ameloblastic fibro-odontoma: a clinicopathologic study of 12 cases.
AB - OBJECTIVE: The ameloblastic fibro-odontoma (AFO) is an uncommon odontogenic tumor
occurring in childhood with limited reported data on recurrence. The purpose of
this AFO study was to review its clinicopathologic features, investigate
treatment modalities and establish a recurrence rate. STUDY DESIGN: The
clinicopathologic features of 12 new cases of AFO were analyzed and compared with
those of 208 cases from the literature, with special emphasis on the clinical
behavior, treatment, and recurrence rate. RESULTS: The average age was 9.4 (+/-
6.7) years with a male-to-female ratio of 1.6:1. The mandible was the site of
occurrence in 59.5%. The tumor most often presented radiographically as a
unilocular mixed density lesion associated with the crown of an impacted tooth.
Displacement of teeth, delayed eruption and bony expansion were commonplace.
There were 5 recurrences among 68 cases with adequate follow-up for a recurrence
rate of 7.4%. All recurrences were attributed to incomplete removal at the time
of the initial surgery. CONCLUSIONS: The AFO is a childhood tumor most often
affecting the posterior jaws and frequently causing bony expansion with profound
affects on the dentition. Conservative surgical removal with extraction of the
associated teeth is recommended. The established recurrence rate is less than
10%.
PMID- 22046700
TI - Chondroid choristoma: report of a rare case.
AB - An 11-year-old girl reported with an intraoral swelling which was noticed by her
mother at birth and increased to its present size during the last year A thorough
clinical examination did not shed a conclusive diagnosis. This case highlights
and discusses the history, clinical features, histologic features, differential
diagnosis and the clinical management of this lesion. Awareness of such an entity
will enrich the knowledge of the pediatric dentists who may be the first ones to
encounter such cases in their day-to-day practice.
PMID- 22046701
TI - Oral manifestation associated with multiple pituitary hormone deficiency and
ectopic neurohypophysis.
AB - Multiple pituitary hormone deficiency (MPHD) is the diminished secretion of all
the hormones produced in the anterior lobe of the pituitary gland. The oral
manifestation of this condition includes delayed eruption and prolonged retention
of primary teeth, delayed formation and eruption of permanent teeth, delay in
development and growth of the jaws, tendency towards development of deep bite and
enamel disturbances. This paper reports the case of an adolescent patient with
MPHD. Clinical examination revealed partial ankylosis and prolonged retention
ofprimary second molars, primary maxillary canines and deep bite. Dental
treatment included extraction of all molars with prolonged retention preceded by
the necessary medical care with clinical and radiographic follow-up afterwards.
The patient was also referred to an orthodontist for orthodontic treatment.
Patients' medical condition should always be investigated by clinicians when
faced with cases of delayed tooth eruption and bone development.
PMID- 22046702
TI - A comparative evaluation of intranasal midazolam, ketamine and their combination
for sedation of young uncooperative pediatric dental patients: a triple blind
randomized crossover trial.
AB - OBJECTIVE: The purpose of this study was to evaluate and compare the efficacy and
safety of intranasal (IN) administration of midazolam (M), ketamine (K) and their
combination (MK) to produce moderate sedation in young, uncooperative pediatric
dental patients. STUDY DESIGN: In this three stage crossover trial forty five
uncooperative ASA type-1 children, who required dental treatment, were randomly
assigned to receive one of the three drugs/combination by IN route during three
subsequent visits. The efficacy and safety of the agents were assessed by overall
success rate and by monitoring of vital signs, respectively. RESULTS: The onset
of sedation was rapid with K as compared to M and MK. The difference was
statistically significant (P < 0.01) between K and M. The overall success rate
was 89% with K, MK was 84% and 69% with M. The difference between the overall
success rates of K and M was statistically significant (P < 0.01). Vital signs
were within physiological limits and there were no significant adverse effects
with any medication. CONCLUSIONS: M, K and MK are safe and effective by IN route
to produce moderate sedation for providing dental care to pediatric dental
patients who have been otherwise indicated for treatment under general
anesthesia.
PMID- 22046703
TI - A digital method to predict the mesiodistal widths of canines and premolars in an
Egyptian sample.
AB - OBJECTIVE: Treatment planning in the mixed dentition is important for proper
tooth alignment. A mixed dentition analysis, should accurately predict the
mesiodistal widths of unerupted permanent teeth. The aim of the present study was
to determine which sum of mesiodistal widths (MDW) of permanent teeth will be the
best predictor for MDW of unerupted permanent canines and premolars. STUDY
DESIGN: The study was conducted on 102 Egyptians, 51 males and 51 females, mean
age 16.7 +/- 0.5 years with fully erupted permanent teeth, and intact proximal
surfaces. Dental casts were obtained and scanned to produce digital images that
were used on a specially designed software program to measure the MDW of
permanent teeth. Casts were divided into training and validation sets, where 9
models of tooth combinations were used to develop a regression equation that
describes the relation between them and sum of MDW of erupted maxillary or
mandibular canines, first and second premolars. The validation set was used to
test the accuracy of the proposed equation. RESULTS: R2 of regression models
ranged from 0.3 (for models #2, 4, 5 and 8) to 0.36for model #1. The highest
regression in model #1 (sum of MDW of lower first permanent molars and upper
central incisors) indicated a high linear association between the sum of MDW of
tooth combination model #1 and the MDWofmaxillary and mandibular permanent
canines and premolars. There was no significant difference between the actual and
the predicted MDW when the proposed equation was checked for its accuracy in the
entire validation set (p > 0.05). CONCLUSION: The combination of the sums of
lower permanent first molars and upper permanent central incisors was the best
predictor for the MD W of both maxillary and mandibular permanent canines and
premolars. The newly proposed prediction equation may be considered clinically
useful for mixed dentition analysis in Egyptian subjects.
PMID- 22046704
TI - Comparison of some dietary habits on corrosion behavior of stainless steel
brackets: an in vitro study.
AB - BACKGROUND AND OBJECTIVE: Resistance to corrosion is an advantageous property of
orthodontic brackets; however, due to low levels of pH found in the mouth of a
patient, localized corrosion may occur This can affect tooth movement by
increasing friction between the arch wire and bracket slot and initiate enamel
discoloration. Additionally, corrosion causes the release of elements that may
lead to cytotoxic and biological side effects. The aim of this study was to
compare the amount of corrosion caused by lemon juice, vinegar and Coca-Cola on
orthodontic brackets in vitro and then to recommend the most suitable diet during
orthodontic treatment. METHOD: Sixty orthodontic brackets in three groups of
twenty were immersed in a test solution (Fusamaya-Meyer artificial saliva plus
lemon juice, vinegar or Coca-Cola) at a temperature of 37 degrees C +/- 1.
Moreover, a negative control consisting of twenty brackets were put in pure
artificial saliva. After 6 weeks the amount of corrosion was determined by
measuring delta W of mean weights of brackets and the results were analyzed by
general linear models (repeated measurement). RESULTS: Significant differences
were seen during different weeks of the study (P < 0.001) and different solutions
(P < 0.001). This study showed the amount of corrosion in orthodontic brackets
was the most for cola followed by vinegar and then lemon juice. In addition, mean
differences for cola versus lemon juice was -0.010 (sig. <0.001), vinegar versus
lemon juice was -0.006 (sig. = 0.001) and cola versus vinegar was -0.004 (sig. =
0.013). CONCLUSION: Acidic effervescent soft drinks such as cola have to be
eliminated or minimized in the nutritional diet of orthodontic patients because
of their harmful effects on their brackets.
PMID- 22046705
TI - Effect of orthodontic appliances on oral microbiota--6 month follow-up.
AB - OBJECTIVE: This study investigates the effect of fixed and removable orthodontic
appliances among children on salivary Streptococcus mutans, Lactobacillus sp. and
Candida albicans. STUDY DESIGN: The study was conducted on 69 patients aged
between 6-17 years who used fixed or removable orthodontic appliances. Five ml
samples of unstimulated saliva from each patient were collected at baseline and
at the 1, 3 and 6 month periodic controls. Samples were diluted and plated on
Mitis Salivarus Agar (MSA), Man Rogosa Sharp Agar (MRS) and Saboroud Dextrose
Agar (SDA). The growths on the plates were examined under a stereomicroscope.
Numbers of colony forming units (CFU) per plate were counted. For statistical
analysis, the paired t test and Chi-Square were used. RESULTS: S mutans and
Lactobacillus sp counts increased significantly 6 months after the insertion of
fixed/removable orthodontic appliances in the oral cavity. A significant increase
for C albicans presence was noted after 3 months compared with baseline for fixed
appliances. CONCLUSION: Long-term utilization of orthodontic appliances may have
a negative effect on microbial flora and increase the risk of new carious lesions
and periodontal problems. Patients should be recalled within short time intervals
to be motivated for oral hygiene during their orthodontic therapy.
PMID- 22046706
TI - [Epidemiology of viral gastroenteritis in France and Europe].
AB - Continuous surveillance of acute diarrhea in France has been conducted by
Inserm's sentinel network of general practitioners (GP) since 1991. Similar GP
based studies have been performed in the Netherlands, Austria and the UK. The
causes of most cases of acute diarrhea are unclear. In case-controlstudies
designed to identify viruses in stools, 35 to 40% of cases and virtually none of
the controls were positive for one of 4 major viruses (rotavirus, calicivirus,
astrovirus and adenovirus). Thus, no viral cause was identified in more than 60%
of patients with acute diarrhea. The causative role of viruses such as torovirus,
picobirnavirus, picornavirus and enterovirus 22 has rarely been investigated.
Further investigations are needed to identify other viral, bacterial fungal or
parasitic causes of acute diarrhea. In France, on average, more than 3 million
people (predominantly children) visit a GP for acute diarrhea each year. Most of
these patients recover spontaneously within a few days, but the medical, social
and economic costs of acute diarrhea are sufficiently high to justify a more
aggressive public policy to prevent and control epidemics in Europe.
PMID- 22046707
TI - [Gastroenteritis viruses in France and Europe].
AB - Rotaviruses and noroviruses are the main causes of acute gastroenteritis in young
children and adults, respectively. Prospective molecular surveillance of
rotavirus genotypes in France and Europe shows that circulating strains may vary
with the season, locality or country. Rotavirus OK? genotypes G1 and G9 are the
most prevalent. Most strains are associated with P[8], showing a certain
genotypic stability of rotaviruses currently circulating in Europe and suggesting
that vaccination would be effective at least in the short and medium term.
However, atypical strains G12 and G8 must be monitored in case they emerge in
future. Noroviruses belong to the Caliciviridae family. These single-stranded RNA
viruses show major genetic diversity. they are divided into 5 genogroups, which
are themselves subdivided into genotypes. In addition, new variants are
continually arising, and are frequently associated with new epidemic waves of
gastroenteritis.
PMID- 22046708
TI - [Viral gastroenteritis in domestic animals and zoonoses].
AB - Etiologic investigations of infectious diarrhea were long limited to bacteria and
protozoa. The advent of electron microscopy and molecular biology showed that
diarrhea could also be caused by viruses, both in humans and in other animals. In
1969, electron microcopy was used to show, for the first time, the responsibility
of a virus in a case of calf diarrhea. This "reo-like virus "was subsequently
identified as a rotavirus, and was shown only four years later to be responsible
for severe diarrhea in young children. Noroviruses, and particularly the human
virus Norwalk, were subsequently discovered, followed by coronavirus, sapovirus,
pestivirus, astrovirus, enteric adenoviruses, torovirus, and picobirnavirus. Some
of viruses found in animals, and particularly rotaviruses, can also infect
humans. Rotaviruses have been identified in numerous animal species and are
generally host-specific, but zoonotic transmission has been suggested by cross
infection (especially in experimental models), by genetic studies showing a close
relationship between certain human and animal rotaviruses, and by the discovery
of new animal genotypes during epidemiological surveillance of human rotaviroses.
Some animal strains of norovirus, sapovirus, picobirnavirus and astrovirus are
genetically related to human strains, but their human transmission has not been
demonstrated.
PMID- 22046709
TI - [Rotavirus vaccination in Europe in 2010].
AB - The important burden of rotavirus infections in infants largely justifies vaccine
prevention. Two attenuated oral vaccines were licensed in Europe in 2006 and have
proven effective against severe rotavirus gastroenteritis in infants, yet few
countries have implemented vaccination. This hesitation may be related to a very
low risk of intussusception in vaccinees, but is mainly due to national
differences in cost-effectiveness.
PMID- 22046710
TI - [Bone microarchitecture].
AB - Bone mass is determined throughout life by modeling and remodeling mechanisms.
Trabecular bone consists of a network of trabeculae (plates and rods) whose
distribution is highly anisotropic: trabeculae are disposed parallel to the
resultant of stress lines (Wolff's law). The trabecular microarchitecture appears
to be conditioned by mechanical stresses exerted on skeletal bones. Few
clinically validated methods are available to assess and monitor the bone
microarchitecture in bone diseases. The best-developed is bone histomorphometry,
with the use of new algorithms to appreciate various 2D characteristics of the
trabeculae, such as thickness and connectivity. Several studies have shown that
several independent techniques should be used to study microarchitecture
parameters. X-ray microtomography (micro CT), microMRI and synchrotron devices
can give non destructive 3D measurements of the trabecular microarchitecture of
bone specimens. This review describes advances in our knowledge of bone
microarchitecture, its role in bone diseases such as osteoporosis, and methods of
2D and 3D histological evaluation.
PMID- 22046711
TI - [Management of osteoporosis: room for improvment].
AB - The objective of anti-osteoporotic treatments is the prevention of the first or
recurrent fractures. Screening of at risk patients is the basis of improvement of
osteoporosis management. Prevalent fractures are strong determinants of incident
fractures. In patients without fractures screening of risk factors, and
quantification of risk using FRAX tool, allows detection of patients who should
receive highest priority for treatment. Several drugs have shown that they are
able to decrease the risk of fracture, providing persistence and compliance. Non
pharmacological approach (including nutrition and physical activity) is part of
optimal management of osteoporosis.
PMID- 22046712
TI - [New actors in bone remodelling: a role for the immune system].
AB - Bone metabolism is mainly under estrogenic control. Estrogen induces the
expression or activation of transcription factors, leading to phenotypic cellular
changes that are critical for the balance between bone formation and resorption.
The two activities are linked via the RANK ligand/osteoprotegerin pathway. Fine
regulation of bone metabolism and the bone-specific response to estrogen
deficiency implies the participation of immune cells, and especially T cells.
Indeed, T cells are activated by estrogen deficiency and produce pro-inflammatory
cytokines such as TNFalpha, which stimulates osteoclastogenesis both directly and
indirectly through the RENKL pathway. Antigen hyperactivity mechanisms may
potentiate T cell activation. Other cytokines such as IL-1 and IL-7 also
participate in the cross-takl between immune cells and osteoclasts. TGFbeta and
IFNgamma modulate these redundant and multiple pathways in a more complex
fashion. B cells may also participate, especially after IL-7-induced activation.
Although many of these findings remain to be validated in humans, they open up
the possibility of new therapeutic approaches, especially given the growing
evidence that post-menopausal osteoporosis is associated with a mild chronic
inflammatory state.
PMID- 22046713
TI - [Advances treatment of osteoporosis: new molecules, new strategies].
AB - Practitioners already have a wide range of effective drugs for the treatment of
osteoporosis, but new options are needed to prevent fractures in patients with
this chronic and disabling disease. Recent advances in bone cell biology have
revealed new specific targets for the treatment of bone loss, based on inhibition
of bone resorption by osteoclasts (anti-RANK ligand antibodies and cathepsin K
inhibitors) or stimulation of bone formation by osteoblasts (anti-sclerostin
antibodies). These future treatments (anti-RANK ligand antibodies should shortly
be available) will add osteoporosis to the growing list of disorders amenable to
targeted biotherapies.
PMID- 22046714
TI - [Spouse violence: treat the bully to save the victim].
AB - Traditionally, the police and judiciary have been rather late in dealing with
domestic violence, considering it to be a private matter. However, this form of
violence has a tendency to increase in frequency and intensity over time. If the
victim's initial complaint is not taken in account, then he or she will become
even more isolated, while the offender may see this" official inaction "as
justifying his or her deeds. The later the authorities call these perpetrators to
book, by reminding them that violence is unacceptable, the more difficult it is
to manage and treat them. This is why, in our jurisdiction (Douai, northern
France), offenders are transiently excluded from the home. Victims are followed
throughout by social workers, who explain the procedure and refer them to a
lawyer if they wish to take legal action. They are also introduced to a self
support group that includes both victims and psychologists, in order to allow
them to share their experience. The public prosecutor encourages the offender to
stay in a designated residential center for about ten days, in order to break the
cycle of abuse. The aim is to stress that all violence is illegal and to give the
offender time to reflect on what led him or her to be violent. After this period
of isolation, the offender, whose behavior is assessed on a standardized form, is
invited to return home, after being informed that any further violence on their
part will lead to an immediate court appearance. Then, during a six-month period,
three hours per week, the offender is invited to attend a self-help group that
includes psychiatrists and psychologists. The results are satisfactory: between
May 2003 and December 2010 the relapse rate stabilized at 6%, a level that seemed
impossible to attain in early 2003 when the system was created
PMID- 22046715
TI - [Rape: a social problem and a public health issue].
AB - The French legal definition of rape was somewhat vague until the 1970s. In
December 1980, the increased awareness created by the feminist movement led to a
precise legal definition and to the possibility for self-help groups to
participate in legal actions. In 1985, a telephone helpline was created after
several rapes were following several rapes committed in public. Since 1986, more
than 39 000 women have called this hotline. Other recent studies confirm the
frequency of rape. Major advances have been made in recent years, in terms of
justice for minors who are victims of rape (lengthening of the statutory
limitation on sexual crimes) and healthcare provision (opening of refuges,
medical-legal consultations, victim management centers, greater awareness among
healthcare professionals, etc.). Women need to be better informed of the
frequency of rape, its legal implications, rapists' strategies, mental disorders,
and the physical (especially gynecological) repercussions of rape. Women must
also be aware that the rapist is the only guilty party. Finally, a
multidisciplinary strategy is needed, notably involving self-help associations
and hospital units that deal with rape victims.
PMID- 22046716
TI - [Contribution of mathematical modeling to vaccination decision making. Examples
from varicella, rotavirus and papillomavirus vaccinations].
AB - The decision to add a new vaccine to the immunization schedule is a complex and
multidisciplinary process based on the risk-benefit balance and, increasingly, on
the cost- effectiveness ratio. Such decisions now use mathematical models that
can predict the indirect, and potentially detrimental, effects of mass
vaccination on the epidemiology of the target disease. The adjunction of an
economic component to the modeling process ensures that vaccination represents an
efficient allocation of available financial resources in an increasingly
constrained environment.
PMID- 22046717
TI - [Diagnostic use of positron emission tomography in France: from the coincidence
gamma-camera to mobile hybrid PET/CT devices].
AB - Positron emission tomography (PET) is a well-established medical imaging method.
PET is increasingly used for diagnostic purposes, especially in oncology. The
most widely used radiopharmaceutical is FDG, a glucose analogue. Other
radiopharmaceuticals have recently been registered or are in development. We
outline technical improvements of PET machines during more than a decade of
clinical use in France. Even though image quality has improved considerably and
PET-CT hybrid machines have emerged, spending per examination has remained
remarkably constant. Replacement and maintenance costs have remained in the range
of 170-190 Euros per examination since 1997, whether early CDET gamma cameras or
the latest time-of-flight PET/CT devices are used. This is mainly due to shorter
acquisition times and more efficient use of FDG New reimbursement rates for
PET/CT are needed in France in order to favor regular acquisition of state-of-the
art devices. One major development is the coupling of PET and MR imaging.
PMID- 22046719
TI - Mitigation of conflicts with automation: use of cognitive countermeasures.
AB - OBJECTIVE: The aim of this study was to empirically assess the efficacy of
cognitive countermeasures based on the technique of information removal to
enhance human operator attentional disengagement abilities when facing
attentional tunneling. BACKGROUND: Lessons learned from human factors studies
suggest that conflict with automation leads to the degradation of operators'
performance by promoting excessive focusing on a single task to the detriment of
the supervision of other critical parameters. METHOD: An experimental setup
composed of a real unmanned ground vehicle and aground station was developed to
test the efficiency of the cognitive countermeasures.The scenario (with and
without countermeasure) involved an authority conflict between the participants
and the robot induced by a battery failure.The effects of the conflict and, in
particular, the impact of cognitive countermeasures on the participants'
cognition and arousal were assessed through heart rate measurement and eye
tracking techniques. RESULTS: In the control group (i.e., no countermeasure), 8
out of 12 participants experienced attentional tunneling when facing the
conflict, leading them to neglect the visual alarms displayed that would have
helped them to understand the evolution of the tactical situation. Participants
in the countermeasure group showed lower heart rates and enhanced attentional
abilities, and 10 out of 11 participants made appropriate decisions. CONCLUSIONS:
The use of cognitive countermeasures appeared to be an efficient means to
mitigate excessive focus issues in the unmanned ground vehicle environment.
APPLICATIONS: The principle of cognitive countermeasures can be applied to a
large domain of applications involving human operators interacting with critical
systems.
PMID- 22046718
TI - Predictors of computer use in community-dwelling, ethnically diverse older
adults.
AB - OBJECTIVE: In this study, we analyzed self-reported computer use, demographic
variables, psychosocial variables, and health and well-being variables collected
from 460 ethnically diverse, community-dwelling elders to investigate the
relationship computer use has with demographics, well-being, and other key
psychosocial variables in older adults. BACKGROUND: Although younger elders with
more education, those who employ active coping strategies, or those who are low
in anxiety levels are thought to use computers at higher rates than do others,
previous research has produced mixed or inconclusive results regarding ethnic,
gender, and psychological factors or has concentrated on computer-specific
psychological factors only (e.g., computer anxiety). Few such studies have
employed large sample sizes or have focused on ethnically diverse populations of
community-dwelling elders. METHOD: With a large number of overlapping predictors,
zero-order analysis alone is poorly equipped to identify variables that are
independently associated with computer use. Accordingly, both zero-order and
stepwise logistic regression analyses were conducted to determine the correlates
of two types of computer use: e-mail and general computer use. RESULTS: Results
indicate that younger age, greater level of education, non-Hispanic ethnicity,
behaviorally active coping style, general physical health, and role-related
emotional health each independently predicted computer usage. CONCLUSION: Study
findings highlight differences in computer usage, especially in regard to
Hispanic ethnicity and specific health and well-being factors. APPLICATION:
Potential applications of this research include future intervention studies,
individualized computer-based activity programming, or customizable software and
user interface design for older adults responsive to a variety of personal
characteristics and capabilities.
PMID- 22046720
TI - The effect of transverse shear force on the required coefficient of friction for
level walking.
AB - OBJECTIVE: An enhanced methodology to extract the required coefficient of
friction (RCOF) value was used to investigate the effects of the transverse shear
component of the ground reaction force (GRF) on the RCOF. BACKGROUND: The RCOF is
an important indicator for slip incidents. However,the extraction of the RCOF
from GRF is not standardized. The transverse shear force is usually ignored in
calculating the RCOF value. METHOD: For this study, 40 participants performed
four walking conditions. The RCOF values both with (RCOF2) and without (RCOF1)
the transverse shear force were identified from each strike by the use of an
enhanced method and were compared. RESULTS: A total of 24,851 strikes were
collected. The transverse component increased the RCOF value by more than 10% in
7.2% of the strikes. In 10.4% of the strikes, the RCOF2 occurred at least 20 ms
earlier and the RCOF value was on average 8.9% larger than RCOF1. CONCLUSION:
With this method, we were able to successfully identify the RCOF in a
significantly large number of strikes across 40 participants. In a portion of the
strikes, the transverse shear force increased the RCOF significantly. In a
significant portion of the strikes, the RCOF2 occurred much earlier than RCOF1.
APPLICATION: Better estimates of the RCOF magnitude and instant of occurrence
could potentially improve risk assessment and identification of critical instants
in gait.
PMID- 22046721
TI - Biomechanical effects of mobile computer location in a vehicle cab.
AB - OBJECTIVE: The objective of this research is to determine the best location to
place a conventional mobile computer supported by a commercially available mount
in a light truck cab. BACKGROUND: U.S. and Canadian electric utility companies
are in the process of integrating mobile computers into their fleet vehicle cabs.
There are no publications on the effect of mobile computer location in a vehicle
cab on biomechanical loading, performance, and subjective assessment. METHOD: The
authors tested four locations of mobile computers in a light truck cab in a
laboratory study to determine how location affected muscle activity of the lower
back and shoulders; joint angles of the shoulders, elbows, and wrist; user
performance; and subjective assessment. A total of 22 participants were tested in
this study. RESULTS: Placing the mobile computer closer to the steering wheel
reduced low back and shoulder muscle activity. Joint angles of the shoulders,
elbows, and wrists were also closer to neutral angle. Biomechanical modeling
revealed substantially less spinal compression and trunk muscle force. In
general, there were no practical differences in performance between the
locations. Subjective assessment indicated that users preferred the mobile
computer to be as close as possible to the steering wheel. CONCLUSION: Locating
the mobile computer close to the steering wheel reduces risk of injuries, such as
low back pain and shoulder tendonitis. APPLICATION: Results from the study can
guide electric utility companies in the installation of mobile computers into
vehicle cabs. Results may also be generalized to other industries that use
trucklike vehicles, such as construction.
PMID- 22046722
TI - Physical fidelity versus cognitive fidelity training in procedural skills
acquisition.
AB - OBJECTIVE: The current study examined whether training simulators for the
acquisition of procedural skills should emphasize physical fidelity or cognitive
fidelity of the task. BACKGROUND: Simulation-based training for acquiring and
practicing procedural skills is becoming widely established. Generally speaking,
these simulators offer technological sophistication but disregard theory-based
design, leaving unanswered the question of what task features should be
represented in the simulators.The authors compared real-world training and two
alternative virtual trainers, one emphasizing physical fidelity and the other
cognitive fidelity of the task. METHOD: Participants were randomly assigned to
one of four training groups in a LEGO assembly task: virtual-physical fidelity,
cognitive fidelity, real world, and control. A posttraining test to assess the
development of procedural skills was conducted. RESULTS: Both the virtual
physical fidelity and cognitive fidelity training methods produced better
performance time than no training at all, as did the real-world training. The
cognitive fidelity training was inferior in terms of test time compared to the
real-world training, whereas the virtual-physical fidelity training was not. In
contrast, only the real-world and the cognitive fidelity groups, and not the
virtual-physical fidelity group, required significantly less time than the
control group for error correction. CONCLUSION: The two training methods have
complementary advantages. APPLICATION: Combining physical fidelity and cognitive
training methods can enhance procedural skills acquisition when real-world
training is not practicable.
PMID- 22046723
TI - Modeling eye gaze patterns in clinician-patient interaction with lag sequential
analysis.
AB - OBJECTIVE: The aim of this study was to examine whether lag sequential analysis
could be used to describe eye gaze orientation between clinicians and patients in
the medical encounter. This topic is particularly important as new technologies
are implemented into multiuser health care settings in which trust is critical
and nonverbal cues are integral to achieving trust. This analysis method could
lead to design guidelines for technologies and more effective assessments of
interventions. BACKGROUND: Nonverbal communication patterns are important aspects
of clinician-patient interactions and may affect patient outcomes. METHOD: The
eye gaze behaviors of clinicians and patients in 110 videotaped medical
encounters were analyzed using the lag sequential method to identify significant
behavior sequences. Lag sequential analysis included both event-based lag and
time-based lag. RESULTS: Results from event-based lag analysis showed that the
patient's gaze followed that of the clinician, whereas the clinician's gaze did
not follow the patient's. Time-based sequential analysis showed that responses
from the patient usually occurred within 2 s after the initial behavior of the
clinician. CONCLUSION: Our data suggest that the clinician's gaze significantly
affects the medical encounter but that the converse is not true. APPLICATION:
Findings from this research have implications for the design of clinical work
systems and modeling interactions. Similar research methods could be used to
identify different behavior patterns in clinical settings (physical layout,
technology, etc.) to facilitate and evaluate clinical work system designs.
PMID- 22046724
TI - A meta-analysis of factors affecting trust in human-robot interaction.
AB - OBJECTIVE: We evaluate and quantify the effects of human, robot, and
environmental factors on perceived trust in human-robot interaction (HRI).
BACKGROUND: To date, reviews of trust in HRI have been qualitative or
descriptive. Our quantitative review provides a fundamental empirical foundation
to advance both theory and practice. METHOD: Meta-analytic methods were applied
to the available literature on trust and HRI. A total of 29 empirical studies
were collected, of which 10 met the selection criteria for correlational analysis
and 11 for experimental analysis. These studies provided 69 correlational and 47
experimental effect sizes. RESULTS: The overall correlational effect size for
trust was r = +0.26,with an experimental effect size of d = +0.71. The effects of
human, robot, and environmental characteristics were examined with an especial
evaluation of the robot dimensions of performance and attribute-based factors.
The robot performance and attributes were the largest contributors to the
development of trust in HRI. Environmental factors played only a moderate role.
CONCLUSION: Factors related to the robot itself, specifically, its performance,
had the greatest current association with trust, and environmental factors were
moderately associated. There was little evidence for effects of human-related
factors. APPLICATION: The findings provide quantitative estimates of human,
robot, and environmental factors influencing HRI trust. Specifically, the current
summary provides effect size estimates that are useful in establishing design and
training guidelines with reference to robot-related factors of HRI trust.
Furthermore, results indicate that improper trust calibration may be mitigated by
the manipulation of robot design. However, many future research needs are
identified.
PMID- 22046725
TI - Shining new light on the Hawthorne illumination experiments.
AB - OBJECTIVE: This study provides an historical and statistical analysis of archival
data from the Hawthorne illumination experiments. BACKGROUND: Previous accounts
of the illumination experiments are fraught with inconsistencies because they
have been based on secondary sources. The general consensus has been that
variations in light levels had no effect on worker productivity at Hawthorne. All
reports and data were thought to have been destroyed, but an archive at Cornell
University was found to contain copies of the original documentation and much of
the data from all three illumination experiments. Conclusions were originally
drawn from visual comparisons of productivity graphs, and the data have never
been properly statistically analyzed. METHOD: Archival reports, notes,
photographs, and letters on the experiments were consulted. Productivity data
were extracted from the tables and graphs in the reports and statistically
analyzed for each experiment. RESULTS: Previously unpublished details of the
illumination experiments emerged. An effect of lighting on productivity was found
in the first treatment sequence for the first experiment, but this finding was
not confirmed in the second sequence or in the second and third experiments.
CONCLUSION: Experimental results provided inconsistent evidence of an association
between light levels and productivity. All three experiments were found to be
seriously flawed. APPLICATION: This study challenges popular accounts of the
"Hawthorne effect," and the shortcomings of these experiments also have
implications for the design of field studies.
PMID- 22046726
TI - Phased training for high-reliability occupations: live-fire exercises for
civilian firefighters.
AB - OBJECTIVE: The aim of this study was to assess whether the stress reduction
effects of phased training culminating in repeated exposure to a stressful
scenario generalize to new scenarios. BACKGROUND: High-reliability occupations
require personnel to operate in stressful situations involving complex
environments, high degrees of uncertainty and time pressure, and severe
consequences for mistakes. One method of training for such environments
culminates in practice in high-fidelity, highly stressful simulations. For some
domains, realism necessitates large-scale, difficult-to-modify physical
simulations. This necessity often results in repeated exposure to one or very few
scenarios. The literature gives reason to question whether the stress reduction
effects of such exposure transfer to new scenarios. METHOD: Anxiety and cognitive
difficulties were measured among firefighter trainees during three live-fire
drills. For each trainee, two drills involved the same scenario, and the other
involved a new scenario that was structurally similar to the repeated scenario.
RESULTS: As predicted, anxiety and cognitive difficulties decreased across
repetitions of the same scenario. However, the reduction did not generalize to a
new scenario, and a nontrivial portion of the sample showed signs of negative
transfer. CONCLUSION: Repeated exposure to the same stressful scenario as the
final phase of training has limited practical value for stress reduction. Methods
for expanding the range of scenarios to which trainees are exposed or for
increasing the value of the exposure are recommended. APPLICATION: The findings
could help improve design of training programs for high-reliability occupations.
PMID- 22046727
TI - Physical and cognitive effects of virtual reality integrated training.
AB - OBJECTIVE: The objective of this study was to evaluate the cognitive and physical
impact of virtual reality (VR) integrated training versus traditional training
methods in the domain of weld training. BACKGROUND: Weld training is very
important in various industries and represents a complex skill set appropriate
for advanced training intervention. As such, there has been a long search for the
most successful and most cost-effective method for training new welders. METHOD:
Participants in this study were randomly assigned to one of two separate training
courses taught by sanctioned American Welding Society certified welding
instructors; the duration of each course was 2 weeks. After completing the
training for a specific weld type, participants were given the opportunity to
test for the corresponding certification. Participants were evaluated in terms of
their cognitive and physical parameters, total training time exposure, and
welding certification awards earned. Each of the four weld types taught in this
study represented distinct levels of difficulty and required the development of
specialized knowledge and skills. RESULTS: This study demonstrated that
participants in the VR integrated training group (VR50) performed as well as, and
in some cases, significantly outperformed, the traditional welding (TW) training
group.The VR50 group was found to have a 41.6% increase in overall certifications
earned compared with the TW group. CONCLUSION: VR technology is a valuable tool
for the production of skilled welders in a shorter time and often with more
highly developed skills than their traditionally trained counterparts.
APPLICATION: These findings strongly support the use ofVR integrated training in
the welding industry.
PMID- 22046728
TI - Twentieth Convocation, Royal Australasian College of Dental Surgeons, Perth,
Western Australia, March 2010. Address by the President of the Royal Australasian
College of Dental Surgeons Bernadette Drummond, BDS, MS, PhD, FRACDS at the
opening ceremony.
PMID- 22046729
TI - Twentieth Convocation, Royal Australasian College of Dental Surgeons, Perth,
Western Australia, March 2010. Opening address by His Excellency Dr Ken Michael,
AC Governor of Western Australia.
PMID- 22046730
TI - Twentieth Convocation, Royal Australasian College of Dental Surgeons Perth,
Western Australia, March 2010. The Fourteenth Robert Harris Oration.
PMID- 22046731
TI - Aesthetics in implant therapy: a blueprint for success and change.
AB - High-end implant aesthetics requires precise steps from diagnosis through surgery
to the restorative phase. These steps are not exclusive of each other. They are
deliberate and require a clear understanding of what is possible and the skills
that are required to carry out each procedure. Every small advancement will help
in the initial and long-term stability of the treatment. This article will
dissect implant treatment into key concepts and procedures, illustrating how
these steps are crucial to a highly successful aesthetic outcome.
PMID- 22046732
TI - They're only baby teeth; who should care?
AB - Despite significant improvements in our understanding of the pathogenesis of
dental caries, it remains one of the most common chronic diseases of childhood.
Given that few very young children actually attend dental health services, there
is a role for non-dental healthcare professionals in the prevention of dental
disease and the promotion of oral health. This presentation will take an evidence
based approach to explore opportunities for increased collaboration between
dental and non-dental healthcare professionals to optimize the health outcomes
for children. The role and responsibilities of the dental profession in
developing this model of shared care will also be discussed.
PMID- 22046733
TI - Molar incisor hypomineralization: clinical management in children.
PMID- 22046734
TI - Bisphosphonates and the dental practitioner--a guide to management.
AB - The author has been managing osteonecrosis of the jaws (ONJ) for more than six
years. This paper will outline the dental management of patients taking
bisphosphonates. This will include: 1. The predisposing factors causing ONJ, 2.
Its clinical presentation, 3. Staging for the appropriate conservative and
surgical management, 4. Guidelines for prevention, 5. Case report.
PMID- 22046735
TI - The use of virtual reality tools in surgical education.
AB - Advances in computing, specifically those used for simulation and games
technology has allowed for exciting developments in dental and surgical
education. At the same time concerns are being raised that students with
relatively little training, practise to improve their skill on patients with all
of the inherent risks that may occur. Simulation in dentistry has been practised
for many years and so the concept is not new to the profession. New tools have
been developed that both enhance teaching and learning and are also useful for
assessment of students and trainees. The challenge of virtual and simulated
reality tools is to have the required fidelity to improve teaching and learning
outcomes over the currently utilized methodology.
PMID- 22046736
TI - Ridge preservation: does it actually work?
AB - Post-extraction the alveolus undergoes modelling which reduces height and width.
This may present a problem for subsequent crown and bridge or implant therapy.
Ridge preservation is the use of grafts and/or membranes to try to minimize the
loss of the alveolar ridge. Extraction sockets have been filled with autogenous,
allogenic and alloplastic materials. Membranes or soft tissue were used to
contain the graft. More recently biodegradable sponges and materials coated in
growth factors have been tested. Studies have primarily looked at either
maintenance of vertical and horizontal dimensions or the healing of the socket
and how much of the graft material is incorporated into the newly formed bone.
Irrespective of method or materials, there seems to be some maintenance of the
alveolus. Bone fill seems to occur in preserved extraction sockets, but in most
cases with a high percentage of residual graft particles. In general, there is a
lack of evidence to show that ridge preservation aids in correct 3-D implant
placement, maintains hard and soft tissue volume over a prolonged period of time
or for success and survival of implants placed into ridge preserved sockets.
Still the most effective way to maintain ridge volume is to keep the natural
tooth.
PMID- 22046737
TI - Novel approaches in 3-dimensional facial profiling to establish facial aesthetic
objectives in the treatment of facial dysmorphologies.
AB - When confronted with facial dysmorphologies, three-dimensional (3D) facial
harmony is preferably assessed with regard to normality. This, however, presents
two major challenges. The first challenge is to define normality. What makes non
dysmorphic faces appear normal? The second challenge is to situate the
craniofacial dysmorphology with respect to normality. What makes the dysmorphic
face not appear to be normal? To tackle these challenges, a novel approach based
on a Face Space is proposed. In essence, faces are represented as points in a
High-dimensional space, the dimensions of which capture important sources of
allowed facial variation within a normal population. To establish an aesthetic
objective of a given dysmorphic face, the novel concept of the "normal
equivalent" of that face via robust projection into the Face Space is proposed.
This technique is demonstrated on an artificial example in which smiling whilst
showing teeth is considered a surrogate for facial dysmorphology.
PMID- 22046738
TI - Aspects of wear and tear of tooth structure.
AB - Lifestyle factors and the increased longevity of the dentition due to greater
life expectancy have resulted in greater wear and tear (cracking) of teeth. Often
there exists interplay between damage and repair. An understanding of these
mechanisms of damage and repair will assist the clinician in correct diagnosis
and treatment planning. Preventive strategies as well as interdisciplinary
measures are required for optimal outcomes. However, are some of our restorative
interventions causing further damage to tooth structure?
PMID- 22046739
TI - General well-being in the new decade--important considerations.
AB - Chronic diseases have created a growing burden of ill-health as populations age,
become more obese and as survival with many conditions improves. Cardiovascular
disease, cancer and anxiety/depression merit priority by being common and
treatable. Genomics aid diagnosis and understanding but have limited impact on
management. Early diagnosis requires comprehensive annual clinical reviews, in
which dental practitioners have an important role. Relevant imaging can be
helpful. Useful early interventions include tactical lifestyle measures, weight
control, appropriate supplements and low dose pharmacotherapy.
PMID- 22046740
TI - IT and security considerations for online clinical records.
AB - E-health and the national electronic medical record are on our doorstep. As an
integral part of the healthcare system, dentistry needs to get on board with this
national initiative. How prepared is the dental profession for this? How can a
culture of online clinical records be promoted and what protocols and
infrastructure exist for this to occur? The lack of government restriction means
that dentistry should be taking full advantage of what is possible. The benefits
and barriers to adoption of online records will be presented to provide a frame
of reference for the next major shift in electronic communication.
PMID- 22046741
TI - Repair of critical size defects in the rabbit calvarium with the use of a novel
scaffold material.
AB - A number of materials have been implanted into skull defects to determine if
improved healing outcomes can be achieved. In some instances, packing or
implanting bone-inducing alloplasts into a standardized skull defect results in
better healing than an untreated defect. AlloDerm is a skin derived acellular
collagen membrane and has characteristics that are known to be effective in
promoting bone growth. It has not been previously investigated for use in cranial
bone healing. The aim of the investigation was to determine if implanting this
novel scaffold into skull defects will improve the quality of bone repair. Six
rabbits received AlloDerm grafts into critical-sized calvarial defects. The
rabbits were sacrificed at two months and the specimens examined histologically
and radiographically. At the time of sacrifice, it was found that while bony
growth had commenced at the margins of the defect and as isolated islands within
the graft, there did not appear to be a major benefit in using the material
described.
PMID- 22046742
TI - Understanding adhesive dentistry.
AB - This review paper firstly provides an outline of the development of resin-based
adhesives. A simple classification method is described based on whether an acid
etching agent requiring a washing and drying step is used. These systems are
called etch and rinse systems. The other adhesives that do not have the washing
and drying steps are referred to as self-etching adhesives. The advantages and
disadvantages of these groups of adhesives are discussed. Methods of adhering to
the tooth surface are provided, especially where the resin-based adhesive
reliability is difficult to control.
PMID- 22046743
TI - The missing link in minimal intervention dentistry: effective caries control.
PMID- 22046744
TI - Osseointegration--the influence of implant surface.
AB - The modification of implant surfaces from the original machined to 'micro-rough',
and more recently 'bioactive', surfaces has been proposed to improve clinical
outcomes. This review outlines the evidence for the superior performance of
modified implant surfaces. Pre-clinical trials consistently show that modified
implant surfaces are more osteogenic and improve the degree of osseointegration.
Clinically, there is a clear trend for improved clinical success with 'micro
rough' compared with machined implants. This is particularly the case in
compromised sites, such as the posterior maxilla, and compromised patients, such
as smokers. Furthermore, 'micro-rough' implant surfaces perform better in
augmented sites, and facilitate the more predictable use of short implants, thus
reducing the need for more invasive augmentation procedures. 'Micro-rough'
implants have been associated with an increased susceptibility to peri
implantitis, but these findings relate to a surface that is no longer
manufactured. Newly developed 'bioactive' surfaces have only been evaluated in a
limited number of clinical studies.
PMID- 22046745
TI - Understanding risk for periodontal disease.
AB - An ability to identify individuals at risk for progressive periodontal disease
would enable targeted prevention and treatment, thus reducing the economic burden
on society. The importance of the interplay between microbial, genetic and
environmental factors in risk assessment is recognized and the relative
contributions of various risk factors has been determined. However, newer
technologies will enable more accurate individual risk profiling in the future.
PMID- 22046746
TI - Coronectomy as the treatment of choice in wisdom teeth showing radiographic signs
of close proximity to inferior dental nerve.
AB - The aim of the study is to compare the prevalence of post-operative inferior
dental nerve (IDN) deficit after coronectomy with total removal of wisdom teeth
showing specific radiographic signs of close proximity to IDN. A randomized
clinical trial comparing total removal and coronectomy of wisdom tooth was
conducted. Analyses of the correlations of IDN deficit and various radiographic
signs of wisdom tooth roots showing close proximity to IDN were performed. Two
radiographic signs were found to be positive predictors ofintra-operative IDN
exposure. Specific radiographic signs or the presence of two or more radiographic
signs are positive predictors of post-operative IDN deficit. The study concluded
that darkening of the wisdom tooth root and presence of two or more specific
signs in radiographs significantly increased the risk of IDN deficit in lower
wisdom tooth surgery. Coronectomy can significantly reduce the prevalence of an
IDN deficit in patients with lower wisdom teeth showing radiographic signs of
close proximity to IDN. It also carries less surgical morbidities when compared
with total removal of lower wisdom tooth.
PMID- 22046747
TI - Early wound healing following a mechanical cleansing post-surgical protocol--a
randomized controlled trial.
PMID- 22046748
TI - Making phytoremediation work better: maximizing a plant's growth potential in the
midst of adversity.
AB - While a number of different plants can either breakdown a variety of organic
contaminants or hyperaccumulate metals from the environment, even the most
efficient of those plants is typically inhibited by the presence of the
toxicant(s). The plant stress that is induced by the presence of various
environmental toxicants typically limits a plant's growth and ultimately its
ability to phytoremediate the toxicant(s). Here, it is argued that the simple
strategy of adding plant growth-promoting bacteria (preferably endophytes) that
reduce plant ethylene levels by ACC deaminase activity and have the ability to
synthesize the phytohoromone IAA, and are used to phytoremediate various
toxicants can significantly (and often dramatically) increase both plant growth
and phytoremediation activity in the presence of those toxicants.
PMID- 22046749
TI - Use of plasma-based spectroscopy and infrared microspectroscopy techniques to
determine the uptake and effects of chromium(III) and chromium(VI) on Parkinsonia
aculeata.
AB - Chromium uptake and tolerance by Mexican Palo Verde (Parkinsonia aculeata) (MPV)
was studied in a six-month experiment with Cr(III) and Cr(VI) at 60 and 10 mg kg(
1), respectively. Chromium and nutrient uptake were determined by ICP-OES and
changes in macromolecules were studied by infrared microspectroscopy (IMS). In
the Cr(VI)-treated plants, chromium concentration increased in the roots only
through the third month, while translocation to stems increased constantly
throughout the six months. Cr(III) applications decreased the amount of Zn in
leaves and stems (p < or = 0.05). Cr(VI) increased P and S in all plant tissues
and increased Ca in roots, but decreased Ca in stems and leaves, and Mg in roots
and stems. Cr(III) decreased P in stems and leaves, while both Cr ions decreased
K in all MPV tissues. Relative to untreated plant tissue, the IMS revealed
significant changes at 1730 cm(-1) and 845 cm(-1). Changes at 1730 cm(-1)
indicated that the cortex and xylem of Cr-treated plants were more proteinaceous.
Changes at 845 cm(-1) revealed higher lignifications in cortex. However, at the
stem level, Cr(VI) decreased lignin deposition in xylem. The data showed that MPV
could be useful in the phytoremediation of Cr in moderately impacted soils.
PMID- 22046750
TI - Phyto (in)stabilization of elements.
AB - The effects of plants (corn, soybean, and sunflower) and fertilizer on mobility
of more than 60 elements were assessed in a greenhouse experiment. Unplanted
columns with the same soil served as controls. Half the columns received
fertilizer and all columns were watered at the same rate. At the end of the
experiment, the columns were watered to mimic a rainstorm event such that water
drained from the bases of the columns, which was collected and analyzed for
element content. Soil from between the roots of the plants was also collected and
the water-extractable fraction determined. It was expected that (1) more mobile
elements, as measured by water extraction, would be leached from the soils at a
higher rate compared to less mobile elements, (2) plants would immobilize most
elements, but that some would be immobilized, and (3) that this would depend on
plant species. The results led to the following conclusions: plants cause metal
mobility to vary over a wide range for a specific soil and do mobilize some
elements (e.g., Th) while immobilizing others (e.g., U). The effects depended on
plant species for some elements. Water-extractable fractions of elements do not
predict mobility.
PMID- 22046751
TI - Copper phytoextraction in tandem with oilseed production using commercial
cultivars and mutant lines of sunflower.
AB - Use of sunflower (Helianthus annuus L.) for Cu phytoextraction and oilseed
production on Cu-contaminated topsoils was investigated in afield trial at a
former wood preservation site. Six commercial cultivars and two mutant lines were
cultivated in plots with and without the addition of compost (5% w/w) and
dolomitic limestone (0.2% w/w). Total soil Cu ranged from 163 to 1170 mg kg(-1).
In soil solutions, Cu concentration varied between 0.16-0.93 mg L(-1). The
amendment increased soil pH, reduced Cu exposure and promoted sunflower growth.
Stem length, shoot and capitulum biomasses, seed yield, and shoot and leaf Cu
concentrations were measured. At low total soil Cu, shoot Cu mineralomass was
higher in commercial cultivars, Le., Salut, Energic, and Countri, whereas
competition and shading affected morphological traits of mutants. Based on shoot
yield (7 Mg DW ha(-1)) and Cu concentration, the highest removal was 59 g Cu ha(
1). At high total soil Cu, shoot Cu mineralomass peaked for mutants (e.g., 52 g
Cu ha(-1) for Mutant 1 line) and cultivars Energic and Countri. Energic seed
yield (3.9 Mg air-DW ha(-1)) would be sufficient to produce oil Phenotype traits
and shoot Cu removal depended on sunflower types and Cu exposure.
PMID- 22046752
TI - Toward protein engineering for phytoremediation: possibilities and challenges.
AB - The combination of rational protein engineering and directed evolution techniques
allow for the redesign of enzymes with tailored properties for use in
environmental remediation. This review summarizes current molecular methods for
either altering or improving protein function and highlights examples of how
these methods can address bioremediation problems. Although much of the protein
engineering applied to environmental clean-up employs microbial systems, there is
great potential for and significant challenges to translating these approaches to
plant systems for phytoremediation purposes. Protein engineering technologies
combined with genomic information and metabolic engineering strategies hold
promise for the design of plants and microbes to remediate organic and inorganic
pollutants.
PMID- 22046753
TI - Exogenous cytokinin treatments of an Ni hyper-accumulator, Alyssum murale, grown
in a serpentine soil: implications for phytoextraction.
AB - Application of exogenous plant growth regulators was examined as a viable
technique to increase the efficiency of plant metal extraction from contaminated
soils. The aim of this study was to investigate the alteration of Ni
phytoextraction by Alyssum murale, a Ni hyperaccumulator, following the
application of cytokinins. The following parameters were investigated: Ni
accumulation, plant growth, gas exchange, stomata behavior and the concentration
of nonprotein thiols (glutathione, y-Glu-Cys, and phytochelatins). In a pot
experiment, A. murale plants grown in a serpentine soil were treated with a mix
of naturally occurring cytokinins. Results showed that Ni accumulation in plants
ranged from 4000 to 7000 mg kg(-1) confirming the hyper-accumulation ability from
the soil used. Cytokinin treatments produced a significant increase in plant
biomass and transpiration rate whereas no significant variation in Ni
accumulation or the concentration of non-protein thiols was observed. The results
suggest that A. murale is a plant species sensitive to cytokinin treatment and
that cytokinin treatment is potentially useful in increasing the phytoextraction
capability by increasing biomass. Moreover, for first time, evidence was obtained
that the Ni hyperaccumulation mechanism is independent of water flux and
transpiration rate.
PMID- 22046754
TI - Opportunities for woody crop production using treated wastewater in Egypt. I.
Afforestation strategies.
AB - The Nile River provides nearly 97% of Egypt's freshwater supply. Egypt's share of
Nile waters is fixed at 55.5 billion cubic meters annually. As a result, Egypt
will not be able to meet increasing water demand using freshwater from the Nile
and has been developing non-conventional wastewater reuse strategies to meet
future demands. The USAID Mission in Cairo began promoting strategies for water
reuse in 2004, and guidelines for safe and direct reuse of treated wastewater for
agricultural purposes were approved in 2005 (Egyptian Code 501/2005). Twenty-four
man-made forests were established that have been useful for assessing the
efficacy of using treated wastewater for afforestation. At present, approximately
4,340 hectares are under irrigation with treated wastewater, utilizing a total
daily volume of 467,400 cubic meters. Wastewater has been applied to trees along
roads, greenbelts in cities, and woody production systems. Currently, a joint
USDA Forest Service--Agricultural Research Service technical assistance team has
been evaluating the feasibility of scaling up such afforestation efforts
throughout Egypt. We describe information about: 1) suitable tree species that
have been identified based on local soil characteristics, water quality, and
quantity of water supply; 2) the benefits and consequences of using these
species; 3) strategies to maximize the potential of afforestation with regard to
improving water quality, maximizing resource production, increasing biodiversity,
and limiting commercial inputs; and 4) potential long-term impacts on the natural
resource base from afforestation. A companion paper addresses irrigation
recommendations based on species and local conditions (see Evett et al. 2000).
PMID- 22046755
TI - Opportunities for woody crop production using treated wastewater in Egypt. II.
Irrigation strategies.
AB - An Egyptian national program targets annual reuse of 2.4 billion m3 of treated
wastewater (TWW) to irrigate 84,000 ha of manmade forests in areas close to
treatment plants and in the desert. To evaluate the feasibility of such
afforestation efforts, we describe information about TWW irrigation strategies
based on (1) water use of different tree species, (2) weather conditions in
different climate zones of Egypt, (3) soil types and available irrigation
systems, and (4) the requirement to avoid deep percolation losses that could lead
to groundwater contamination. We conclude that drip irrigation systems are
preferred, that they should in most cases use multiple emitters per tree in order
to increase wetted area and decrease depth of water penetration, that deep
rooting should be encouraged, and that in most situations irrigation system
automation is desirable to achieve several small irrigations per day in order to
avoid deep percolation losses. We describe directed research necessary to fill
knowledge gaps about depth of rooting of different species in sandy Egyptian
soils and environments, tree crop coefficients needed for rational irrigation
scheduling, and depth of water penetration under different irrigation system
designs. A companion paper addresses recommendations for afforestation strategies
(see Zalesny et al. 2011, this issue).
PMID- 22046756
TI - Quantification of prairie restoration for phytostability at a remediated defense
plant.
AB - In June 2008 and 2009, cover, density, and species diversity were measured on two
areas of the prairie at the U. S. Department of Energy Weldon Spring Site to
begin quantification of the prairie establishment and the effects of a prairie
burn. Sampling began by testing for the most appropriate transect length (cover)
and quadrat size (density) for quantification of vegetation. Total cover
increased in the first growing season after burning. Conversely, total cover
decreased in the unburned area in one year. The trend in litter cover is the
opposite with litter decreasing after burning, but increasing in one year in the
unburned area. Bare ground decreased in one year in the unburned area, but was
unchanged after burning. Species diversity tripled after fire, but was unchanged
in one year in the unburned area. The results show that litter and fire both
affect plant cover. If land reclamation activities are to be an integral part of
hazardous waste remediation at contaminated sites, then the success of
reclamation efforts needs to be quantified along with success criteria for waste
remediation of the sites. The results show that plant cover can be easily
quantified, but that density measures are more biased which makes it more
difficult to achieve adequate sample size for plant density.
PMID- 22046757
TI - Effect of calcium on growth performance and essential oil of vetiver grass
(Chrysopogon zizanioides) grown on lead contaminated soils.
AB - The aim of this study was to investigate effect of calcium on growth, survival,
essential oil yield and chemical compositions of vetiver grass grown on lead
contaminated soils. Calcium inform of CaCO3 (0, 2000, 4000, 6000 mg Ca kg(-1))
was added to river sand soils containing 4000 mg Pb kg(-1) dry soil. Results
showed that, in the absence of calcium treatment, no plants survived after 2
weeks of cultivation, while the rest grew well to the end of the experimental
period (42 weeks). Calcium treatments generally resulted in a slight decrease in
biomass. Interestingly, an increase in calcium over 2000 mg kg(-1) did not result
in a decrease in accumulation of lead in vetiver roots and shoots. The levels of
lead in roots and shoots under calcium treatments were around 2000 and 90 mg kg(
1) dry weight, respectively. The addition of CaCO3 did not improve vetiver
essential oil yield and chemical composition compared to the control. A level of
applied CaCO3 about half of the lead concentration in soils was sufficient to
improve vetiver growth and survival, and accumulate high concentrations of lead
in the roots. This finding can be applied for re-vegetation of lead contaminated
soils using vetiver.
PMID- 22046758
TI - Selenium accumulation in plants--phytotechnological applications and ecological
implications.
AB - Selenium (Se) is an essential trace element for many organisms including humans,
yet toxic at higher levels. Both Se deficiency and toxicity are problems
worldwide. Since plants readily accumulate and volatilize Se, they may be used
both as a source of dietary Se and for removing excess Se from the environment.
Plant species differ in their capacity to metabolize and accumulate Se, from non
Se accumulators (< 100 mg Se/kg DW), to Se-accumulators (100-1000 mg Se/kg DW) to
Se hyperaccumulators (> 1,000 mg Se/kg DW). Here we review plant mechanisms of Se
metabolism in these various plant types. We also summarize results from genetic
engineering that have led to enhanced plant Se accumulation, volatilization,
and/or tolerance, including field studies. Before using Se-accumulating plants at
a large scale we need to evaluate the ecological implications. Research so far
indicates that plant Se accumulation significantly affects the plant's ecological
interactions below and above ground. Selenium canprotect plants from fungal
pathogens and from a variety of invertebrate and vertebrate herbivores, due to
both deterrence and toxicity. However, specialist (Se-tolerant herbivores),
detritivores and endophytes appear to utilize Se hyperaccumulator plants as a
resource. These findings are relevant for managing phytoremediation of Se and
similar elements.
PMID- 22046759
TI - Suspended solids in and turbidity of runoff from green roofs.
AB - Green roof technology is used to reduce the quantity of stormwater runoff, but
questions remain regarding its impact on quality. This study analyzed the total
suspended solids (TSS) in and the turbidity of runoff from green roof growth
media mixed with composted pine bark in an indoor pot study. The results showed
that there were elevated levels of TSS and turbidity in the runoff that decreased
over time for all growth media. Both TSS and turbidity are affected by the type
of growth media. Lava and haydite had higher mean TSS and mean turbidity than
arkalyte and bottom ash. Vegetation reduced the mean turbidity and mean TSS of
the first flush by an average of 53% and 63%, respectively, but generally had no
statistically significant effect thereafter. The results indicate that the media,
rather than the vegetation, has a greater effect on TSS and turbidity in the
runoff In areas with stringent water quality regulations for stormwater runoff
from developed sites, media selection may be an important consideration. It may
also be necessary in these regions to ensure that the roof is planted prior to
receiving rainfall to minimize the first flush effect and that any irrigation
does not result in runoff.
PMID- 22046760
TI - Short rotation coppice culture of willows and poplars as energy crops on metal
contaminated agricultural soils.
AB - Phytoremediation, more precisely phytoextraction, has been placed forward as an
environmental friendly remediation technique, that can gradually reduce increased
soil metal concentrations, in particular the bioavailable fractions. The aim of
this study was to investigate the possibilities of growing willows and poplars
under short rotation coppice (SRC) on an acid, poor, sandy metal contaminated
soil, to combine in this way soil remediation by phytoextraction on one hand, and
production of biomass for energy purposes on the other. Above ground biomass
productivities were low for poplars to moderate for willows, which was not
surprising, taking into account the soil conditions that are not very favorable
for growth of these trees. Calculated phytoextraction efficiency was much longer
for poplars than these for willows. We calculated that for phytoextraction in
this particular case it would take at least 36 years to reach the legal threshold
values for cadmium, but in combination with production of feedstock for bioenergy
processes, this type of land use can offer an alternative income for local
farmers. Based on the data of the first growing cycle, for this particular case,
SRC of willows should be recommended.
PMID- 22046761
TI - Developing a sustainable phytomanagement strategy for excessive selenium in
western United States and India.
AB - Phytomanagement technology is recognized as an inexpensive and environmental
friendly strategy for managing natural-occurring selenium (Se) in soils and in
poor quality waters. Multi-year field and greenhouse studies were conducted with
different plant species in California, USA and Punjab, India under high Se
growing conditions. Some of the plant species included; canola (Brassica napus),
mustard (B. juncea), broccoli (B. oleracea), spearmint (Mentha viridis),
sugarcane (Saccharum officcinarum), guar (Cyamopsis tetragonoloba), wheat
(Triticum aestivum), and poplar (Populus deltoides). California soils had a
sodium-sulfate-dominated salinity between 6-10 dS m(-1), while Indian soils had a
calcium carbonate salinity less than 1 dS m(-1). Results demonstrated that high
sulfate conditions reduced plant Se accumulation more than 100 x in Californian
grown plants compared to Se accumulation in Indian grown plants. Tissue
concentrations generally did not exceed 10 and 200 mg kg DM(-1) in leaves of
plants grown in California and India, respectively. At these plant
concentrations, Se phytomanagement is more effective in Indian soils than in
California soils. Successful management of Se by plants requires selecting crops
or crop rotations that are tolerant of the soil condition and identifying and
creating new viable Se-enriched products.
PMID- 22046762
TI - Nickel solubilizing capacity and characterization of rhizobacteria isolated from
hyperaccumulating and non-hyperaccumulating subspecies of Alyssum serpyllifolium.
AB - Bacterial strains were isolated from the rhizosphere of three populations of the
Ni-hyperaccumulator Alyssum serpyllifolium subsp. lusitanicum (A. pintodasilvae;
M, S, and L), one population of Ni-hyperaccumulator A. serpyllifolium subsp.
malacitanum (A. malacitanum; SB), and one population of the non-hyperaccumulator
A. serpyllifolium subsp. serpyllifolium (A. serpyllifolium; SN). Isolates were
characterized genotypically by BOX-PCR genomic DNA fingerprinting and comparative
sequence analysis of partial 16S rRNA gene, and phenotypically by their Ni
tolerance (0-10 mM), presence of plant growth promoting traits (indoleacetic acid
(IAA)-, siderophore-, or organic acid-production, and phosphate solubilization)
or capacity to produce biosurfactants. Among the collection of rhizobacteria, 84
strains were selected (according to their BOX-PCR profiles and phenotypic
characteristics) to assess their ability to modify Ni extractability from Ni-rich
(serpentine) soils. Metabolites produced by 13 of the isolates mobilized soil Ni
(originating from the rhizosphere of both Ni-hyperaccumulators and non
hyperaccumulator). In contrast, Ni extraction using culture medium filtrates
which had supported the growth of 29 strains was significantly reduced. The
remaining strains had no effect on Ni mobility. Bacterial induced Ni mobilization
was not related to Ni resistance or the phenotypic traits tested. Isolates with
potential use in phytoremediation techniques will be further studied in a plant
microorganism-soil system.
PMID- 22046763
TI - In situ assessment of phytotechnologies for multicontaminated soil management.
AB - Due to human activities, large volumes of soils are contaminated with organic
pollutants such as polycyclic aromatic hydrocarbons, and very often by metallic
pollutants as well. Multipolluted soils are therefore a key concern for
remediation. This work presents a long-term evaluation of the fate and
environmental impact of the organic and metallic contaminants of an industrially
polluted soil under natural and plant-assisted conditions. A field trial was
followed for four years according to six treatments in four replicates:
unplanted, planted with alfalfa with or without mycorrhizal inoculation, planted
with Noccaea caerulescens, naturally colonized by indigenous plants, and
thermally treated soil planted with alfalfa. Leaching water volumes and
composition, PAH concentrations in soil and solutions, soil fauna and microbial
diversity, soil and solution toxicity using standardized bioassays, plant
biomass, mycorrhizal colonization, were monitored. Results showed that plant
cover alone did not affect total contaminant concentrations in soil. However, it
was most efficient in improving the contamination impact on the environment and
in increasing the biological diversity. Leaching water quality remained an issue
because of its high toxicity shown by micro-algae testing. In this matter, prior
treatment of the soil by thermal desorption proved to be the only effective
treatment.
PMID- 22046764
TI - Transgenic plants for phytoremediation.
AB - Phytoremediation is a green, sustainable and promising solution to problems of
environmental contamination. It entails the use of plants for uptake,
sequestration, detoxification or volatilization of inorganic and organic
pollutants from soils, water, sediments and possibly air. Phytoremediation was
born from the observation that plants possessed physiological properties useful
for environmental remediation. This was shortly followed by the application of
breeding techniques and artificial selection to genetically improve some of the
more promising and interesting species. Now, after nearly 20 years of research,
transgenic plants for phytoremediation have been produced, but none have reached
commercial existence. Three main approaches have been developed: (1)
transformation with genes from other organisms (mammals, bacteria, etc.); (2)
transformation with genes from other plant species; and (3) overexpression of
genes from the same plant species. Many encouraging results have been reported,
even though in some instances results have been contrary to expectations. This
review will illustrate the main examples with a critical discussion of what we
have learnt from them.
PMID- 22046765
TI - [The true history of the first immortal cell lines of human origin].
PMID- 22046766
TI - [Cardiorenal syndrome].
AB - Cardiac and renal disease are common and frequently coexist, resulting in
increased risk of mortality, morbidity and cost of care. The interaction between
heart and kidney is refered to as cardiorenal syndrome, but a consensus
definition has not been established. Also, there are limited data about the true
incidence, the pathophisiology is poorly understood and standardized diagnostic
criteria are lacking. Because the process is complex, treatment can be a
challenge despite the novel therapies. This paper addresses all the complex
interactive aspects of the cardiorenal relationship, from pathophysiology to
epidemiology, diagnosis and treatment, to have more clear perspectives on the
future therapeutic approaches to this deadly association.
PMID- 22046767
TI - [Beta-lactamases...until when?].
AB - Due to environmental factors and wide use of antimicrobials, only those species
that developed their own defense mechanisms shall survive. Enzymatic inactivation
is the most common cause of antibiotic resistance. Beta-lactamase production has
been described early after the discovery of penicillin and it continues to
diversify being now able to inactivate even the most advanced antibiotic. The
association with other resistance determinants makes the infection with this kind
of bacteria a major therapeutic problem.
PMID- 22046768
TI - [Clostridium difficile infections: what is new?].
AB - C. difficile is the most common infectious cause of healthcare-associated
diarrhea but now is increasingly recognized as a cause of diarrhea in outpatients
and persons without apparent health care contacts. Emergence and spread of new
epidemic clones of C. difficile 027 (PCR-ribotype) and 078/126 (toxinotype) with
increase toxin production, an aditional binary toxin and high level resistance to
fluoroquinolones and increasing incidence of more rapidly progressive severe
disease, require prompt clinical recognition and new tools to predict severity
and to prevent recurrences. Although antibiotics are effective at inhibiting C.
difficile and treating symptoms, these drugs could not reestablish normal bowel
flora and the rate of recurrences is 25%. During the past years we assisted to an
impressive search for new and more effective therapy that shoud be save, with low
potential for the development of resistance, with low levels of systemic
absorbtion and high levels of active drug in the colon and should be associated
with a low rate of recurrence after treatment. By consequence, different
approaches to the management of recurrent infections have been studied such as
new antibiotics (fidaxomicin), human monoclonal antibodies against C. difficile
toxins A and B, intravenous human immunoglobulin, active immunization, and
probiotic therapy.
PMID- 22046769
TI - Respiratory involvement in the gastroesophageal reflux disesease.
AB - The pathological gastroesophageal reflux disease may lead to the gastroesophageal
reflux disease (GERD), manifested as a spectrum of conditions including erosive
esophagitis, Barrett esophagus and has been linked to the development of
adenocarcinoma of the esophagus. The gastroesophageal reflux has been
incriminated in the occurence of a number of pulmonary symptoms and diseases,
otolaryngologic symptoms, and other extraesophageal manifestations. Clinicians
must be aware of the possibility of some extraesophageal reflux-related
manifestations, even in the absence of heartburn and acid reflux, classic
esophageal symptoms of GERD. Although the correlation between gastroesophageal
reflux disease and the extraesophageal manifestations has been established, a
cause-and-effect relationship has not been proved yet. In this article, we
present the respiratory manifestations of gastroesophageal reflux disease,
referring to epidemiology, pathogenesis, diagnosis and treatment.
PMID- 22046770
TI - [Contributions to the implementation of screening tests for assessing the
neuropsychic development in children].
AB - Currently, in Romania the general practitioner does not use screening tests to
detect the developmental problems in children. That might be the reason why many
cases are diagnosed too late. AIM: To evaluate the impact and the usefulness of a
screening tool for neurodevelopmental disorders in primary care. MATERIAL AND
METHODS: This trans-sequential study was carried out a on a series of 324
children under the age of 5 in the interval January 2007-December 2010. The
neurodevelopmental status of the children was assessed by two methods: routine
clinical assessment, and ASQ screening tools. RESULTS: Compared to routine
assessment, by which 33 children (10,2%) with development delays have been
detected, the use of parent-addressed questionnaires raised the detection
percentage to 12% (6 more children). The use of parent-addressed questionnaires
also improved the doctor-patient communication, increased the degree of parental
involvement in their child's development stimulation, especially with regard to
the malfunctions in verbal and cognitive behavior. CONCLUSIONS: The use of
validated screening tests is a goal for improving the primary care practice.
PMID- 22046771
TI - [Liver cirrhosis--procoagulant stasis].
AB - Abnormal hemostasis tests and bleeding are often associated in liver cirrhosis.
In these patients the balance between hypo- and hypercoagulation status is more
fragile than in healthy people. In the hemostatic abnormalities associated with
chronic liver disease are two main chategory factors: favoring hemorrage and
favoring thrombosis. The main factors that favoring hemorrage are: low platelet
count, impaired platelet function, decreased levels coagulation factors (II, V,
VII, IX, X, XI), quantitative and qualitative abnormalities of fibrinogen,
vitamin K defiency, low levels of trombin activable fibrinolisis inhibitor,
activat plasminogenic tisular. The factors favoring thrombosis are elevated
levels of factors VIII and von Willebrand, decreased levels of protein C, protein
S, antithrombin, decreased levels of plasminogen. Traditionally it was thought
that arterial and venous thrombosis is rare events in cirrhotic patients but
recent studies have indicated that thrombotic complications can paradoxically
occur even if clinically an increased risk of hemorrhage is considered. Treatment
of venous thrombosis in patients with cirrhosis using routine anticoagulation
with heparin and vitamin K antagonists has been described but with a high level
of bleeding complications. So, based on the limited data available, AASLD
guidelines stated no recommendations for or against the use of anticoagulation in
cirrhotic patients with portal thrombosis. Although abnormal hemostasis tests and
bleeding are often associated in patients with chronic liver disease it is a
relatively poor correlation between hemorrhagic risk and routine diagnostic tests
of hemostasis. Management of bleeding complications in liver cirrhosis varies and
no general guidelines are available. The main therapeutic strategies are: red
cell concentrate, plasma, platelet concentrate, recombinant factor VIIa, factor
concentrates, desmopressin, antifibrynolitic agents, thrombopoietin receptor
agonists, antibiotics. Clinical studies examining safety and efficacy of the
various products for the different bleedeing or trombotic complications of liver
cirrhosis need to be initiaded.
PMID- 22046772
TI - Antibiotic prophylaxis considering patient outcome from percutaneous endoscopic
gastrostomy.
AB - OBJECTIVES: The main indications for PEG insertions are the following:
stroke/CVA/diffuse cerebral vascular disease, neurological conditions, e.g. head
injury, motor neurone disease, Multiple Sclerosis etc. Peristomal infection can
sometimes complicate PEG placement. Antibiotics, either prophylaxis or
concurrent, can reduce the incidence of peristomal wound infection after PEG
placement. MATERIAL AND METHOD: Seventy five patients outcome from Percutaneous
Endoscopic Gastrostomy (PEG) were analysed in the period: September 1999 and
October 2007 to the West Cumberland Hospital, Whitehaven (WCH) United Kingdom.
This paper was done to evaluate the practice in WCH and the outcome has helped us
to implement the changes successfully to conform to the guidelines set out by the
British Association of Gastroenterologists. Our main objectives were to evaluate
the antibiotic prophylaxis, the procedure and post procedure complications and
the deaths after PEG tube insertion. CONCLUSIONS: No immediate procedure
complications; Infection was the most common postoperative complication;
Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal
wound infection after PEG placement; Early PEG placement facilitates their
transfer to a non-acute care environment.
PMID- 22046773
TI - [Colorectal cancer--clinical course, epidemiologic and pathologic aspects].
AB - In the past 3 years colorectal cancer became the second cause death (after the
broncho-pulmonary cancer) exceeding gastric cancer by 4150 deaths in 2002 (19,05
per hundred thousand inhabitants) and 4860 deaths in 2006. MATERIAL AND METHODS:
644 of the 18,978 patients coloscopically investigated at the lasi
Gastroenterology and Hepatology Institute in the interval 2000-2007 in which
pathology results revealed colorectal cancer, and 279 patients operated at the
First Clinic Surgery of the Iasi "Sf. Spiridon" Hospital during 2008-2010 were
selected for this study. RESULTS: Colorectal carcinoma has a high incidence in
the patients over 60 years. Sex distribution of the tumors showed that this
disease most commonly affects males. The male/female ratio was 1.3. In less than
3% of the cases the disease occurred at ages under 40 years. The most frequent
clinical manifestations were intestinal transit disorder (97%), pain syndrome on
the left side of the abdomen (82.82%), and progressive severe constipation
(67.89%). 24.07% of the colorectal cancer cases were located at the level of the
proximal colon (cecum, ascending colon, hepatic flexure, transverse colon and
splenic flexure), while 75.9% were located at the distal level. The most frequent
macroscopic form was the vegetative one (89.91%).
PMID- 22046774
TI - [Cross-sectional study to evaluate risk factors in infant malnutrition].
AB - Malnutrition is a major health problem in our country by maintaining a high
number of infants with poor nutritional status. Various studies have highlighted
the role of infant's malnutrition in the development of adult diseases. METHODS:
We made a cross-sectional study during six months (October 2010 - March 2011) on
a group of 63 infants admitted in Pediatric Recovery Department-Children's
Hospital, Iasi; we evaluated the presence of risk factors for malnutrition. The
data were processed using SPSS 16 and Epilnfo 3.5.2. (December 2010). RESULTS:
The infants were predominantly female (52,4%); the most affected age group was 5
24 weeks (84,11%). Most of them came from rural areas (79,4%), from families with
low socioeconomic income (95,2%), mothers with a low educational status (63,4%),
housewives (88,9%). We noted the presence of previous diseases in 71,4% infants.
Only 12 infants received breast milk for a short time (three weeks), the other 51
infants have been bottle-fed since birth. Complementary food was incorrect in
68,42% cases. With a proper diet the mean weight gain was 895,68 g and the Z
score values (weight for age, height for age, weight for height) have improved
during an average of 34,15 days; positive correlation between these factors is
strong. CONCLUSIONS: Low socio-economic income, rural areas, low maternal
educational level, diet errors, small infants with multiple previous diseases are
the main risk factors in malnutrition's occurrence. We consider particularly
important to solve social problems too, not only the medical, because when the
infant returns in the same disadvantaged family there is an increased risk for
malnutrition to recur.
PMID- 22046775
TI - [Correlations between anthropometric parameters and cardio-vascular risk factors
related to lifestyle in a rural population].
AB - BACKGROUND AND AIMS: Prevention and reduction of cardio-vascular mortality are in
relationship with understanding and being able to modify risk factors, among
which overweight and obesity become the most significant. The aim of this paper
is to define cardio-metabolic risk factors which are specific to the studied
population, and also to find elements of lifestyle that lead to overweight. We
targeted smoking, alcohol consumption, stress, physical exercise, income and
educational level. MATERIAL AND METHODS: We studied a sample of 172 subjects,
representative for the population of Deleni, a rural community in Iasi County;
among these subjects, 67 were men, 105 were women, with an average age of 54. For
each a chart was filled, containing demographic data, socio-economic status,
personal and family medical history. We measured anthropometric parameters:
weight (W), height (H), waist circumference (WC) and we calculated body mass
index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). We
performed interviews to fill in a food frequency questionnaire, the Perceived
Stress Scale and the International Physical Activity Questionnaire. RESULTS: In
the lot studied, 44.2% are overweight and 18.6% are obese, the majority of these
being women. Regarding WC, among normal weight, 52.4% have large WC (> or = 94cm
for men and > or = 80cm for women). Obesity markers positively correlate with
increase in age and decrease in income (p=0.024), with low educational level,
regular consumption of coffee (p=0.093), and negatively correlate with excessive
alcohol consumption (p=0.049) and smoking (p=0.003). As expected, there is an
inverse relationship between increased physical exercise and BMI (p=0.015) and a
direct relationship between increased stress level and WC. CONCLUSIONS:
Anthropometric parameters are sensible markers in evaluating the influence of
lifestyle on cardio-metabolic risk.
PMID- 22046776
TI - [Etiological aspects of acute gastroenteritis--a ten-year review (1.01. 2001
31.12.2010)].
AB - Acute gastroentritis is one of the most common diseases in humans, and continues
to be a significant cause of morbidity worldwide. AIMS: To determine the
bacterial pathogens associated with gastroenteritis in patients admitted to the
Iasi Infectious Diseases Hospital in the last ten years. MATERIAL AND METHODS: A
total of 40481 stool samples were examined using conventional methods. RESULTS:
Bacteria were found in 7.36% of cases, and parasites in 9.64%; 83% of the cases
were viral, micotic, or disbiotic. The bacterial etiology was dominated by
Salmonella spp. (58.34%), Shigella spp. (27.08%), Yersinia enterocolitica 03
(8.53%), Campylobacter spp. (1.31%), other bacterial pathogens (EPEC, Aeromonas
hydrophilla/caviae/sobria, Plesiomonas shigelloides, Bacillus cereus,
Staphylococcus aureus, etc) being detected in 3.74% of the cases. Of the
Salmonella species, group B (51.99%) followed by group D (45.23%) were most
common. Shigella sonnei and Shigella flexneri were found in almost the same
proportion (49.45% and 49.70%, respectively); Shigella boydii was isolated in
only 0.85% of cases. The trend of gastroenteritis caused by bacterial pathogens
is decreasing: from 355 cases in 2001 to 105 cases in 2010; three peaks have been
recorded in 2002, 2005 (when Salmonella typhi was isolated in a patient), and
2008 (469, 409, and 252 cases, respectively). Bacterial gastroenteritis affected
both sexes almost equally (122 males and 118 females). The most affected age
groups were: 0 - 4 years, 15 - 24 years, 5 - 14 years and 25 - 39 years.
CONCLUSIONS: Laboratory investigations are essential in determining the etiology
of gastroenteritis. Its unpredictable incidence justifies the human and material
efforts aimed at controlling the spread of potentially epidemic acute
gastroenteritis.
PMID- 22046777
TI - [Monitoring of Mycobacterium tuberculosis infections in Iasi County in 2009].
AB - Tuberculosis is a major public health problem worldwide. Our study aimed to
investigate epidemiological and demographic characteristics of tuberculosis
infection and resistance to antituberculous drugs in Iasi County in 2009.
MATERIAL AND METHOD: We have analysed the epidemiological parameters for 687
patients with pulmonary tuberculosis, new cases confirmed by microscopy and
cultivation on Lowenstein Jensen. First and second-line antituberculous
susceptibility testing was done for 130 strains, using agar proportion method and
absolute-concentration method. RESULTS: The number of new cases of tuberculosis
was higher in rural areas and in males 41-50 years old (sex ratio=2.22). The
proportion of positive cases in microscopy was 81.51%. Drug resistance was as
follows: 16 isolates (12.3%) to isoniazid, 5 (3.84%) to rifampin, 2 (1.53%) to
ethambutol, 2 (1.53%) to streptomycin and 4 (3.07%) were multidrug-resistant.
CONCLUSIONS: In this study we found high resistance rates to isoniazid,
streptomycin and ethambutol. This requires increasing efficiency of tuberculosis
diagnosis and susceptibility testing.
PMID- 22046778
TI - [Bone mineral density in patients with rheumatoid arthritis].
AB - Patients with rheumatoid arthritis (RA), an immune-mediated inflammatory
rheumatic disease with peripheral and systemic involvement, are at increased risk
of bone loss and fractures. There are many reasons for the high prevalence of
osteoporosis (OP) in RA, including both traditional and specific risk factors
such as pain and loss of joint function, medication (corticosteroids,
methotrexate), and increased proinflammatory cytokines. AIM: To evaluate bone
mineral density status in RA patients, focusing on potential relation with
classical risk factors for OP. MATERIAL AND METHODS: One-year prospective
observational study on 83 consecutive postmenopausal women, 43 diagnosed with RA
(group I), and 40 healthy controls (group II) with no previous condition and
medication known to affect bone metabolism and turnover. Bone mineral density
(BMD) and T-score evaluated by dual X-ray absorbtiometry (DXA) at three standard
skeletal sites (L1-L4 lumbar spine, hip and forearm) (Hologique QDR 100 device),
and classical risk factors for osteoporosis were assessed in all patients
according to a predefined protocol. Data were analyzed in SPSS-13 using ANOVA, t
Student, chi-square and ROC (Receiver Operator Characteristic). RESULTS:
Decreased BMD was reported in the majority of RA cases, mainly in the spine and
femoral neck (86%), but also in total hip (72%); moreover, osteoporosis was
commonly demonstrated in lumbar spine and osteopenia at hip level. Statistically
significant differences between diagnostic categories (normal, osteopenia,
osteoporosis, WHO 1994) (p<0.05), while no significant differences between mean
BMD levels in women with and without RA at different skeletal sites were found (t
student, p>0.05). However, considerable BMD variation (51.7% to 102.3%) was
suggested in RA as compared to non-RA patients (14.3% to 27%) (ANOVA).
Significant differences in mean T-score at total hip and forearm (mainly 33%
radius) were noted in patients with and without RA (p<0.05). No relation between
osteodensitometric parameters and classical risk factors for OP has been
identified in RA, except menopause. Indirect weak statistically significant
correlations were found between mean T-score and menopause duration at all
skeletal levels (Pearson's rank correlation, p<0.05), except for the femoral neck
(r=+0.03, p<0.05). CONCLUSIONS: Decreased BMD is commonly seen in RA patients.
Several characteristics based on DXA assessment have been identified, including
preference for distinct skeletal sites (spine, hip, distal forearm), and the
particular intervention of menopause.
PMID- 22046779
TI - [Detection of fusion gene--integral part of the assessment of children with acute
leukemia].
AB - Acute leukemia is the most common malignancy in children, being mostly produced
by such chromosomal abnormalities as translocations or inversions causing gene
fusion. Different clinical studies showed that translocations identified in ALL
(acute lymphoblastic leukemia) and AML (acute myeloblastic leukemia) may be used
to classify patients into risk groups. AIM: To detect three fusion genes that
have been proven very important in patient classification: t(9:22)p190, t(4:11)
and t(12:21). MATERIAL AND METHOD: We conducted a prospective study on 30
patients with acute leukemia diagnosed in the interval September 2009 - September
2010 at the Iasi Hemato-Oncology Unit of Saint Mary Hospital for Children.
RESULTS: We found t(9:22)p190 in two patients, t(4:11) in two patients and
t(12:21) in one patient. From the total of 30 patients, 7 were considered at high
risk, 3 were diagnosed with AML, and 20 were considered at standard-risk.
CONCLUSIONS: Day 33 can still be considered the reference time in the evaluation
of treatment response; patients with BCR-ABL seem to have a worse prognosis than
those who do not have this translocation. The detection of fusion genes is very
important in patient classification.
PMID- 22046780
TI - [Characteristics of hepatitis C virus (HCV) infection in closed communities].
AB - AIM: To determine the prevalence of HCV in closed communities and the relations
between risk behavior and HCV infection. MATERIAL AND METHODS: The persons
deprived of personal freedom selected for this study have filled out an epidemio
logical questionnaire including identity and epidemiological data (detention
history, evaluation of the risk factors), as well as a written consent. All the
subjects were tested for the presence of anti-HCV antibodies. RESULTS: This study
included 326 of the total of 500 persons deprived of personal freedoms at the
Bacau Correctional Facility The prevalence of hepatitis B and C was 15.34 %, and
that of HCV 5.21%, higher than in the general population. Risk factors associated
with HCV in closed communities were injected drugs, homosexuality, and tattooing.
CONCLUSIONS: The results confirm that the population in correctional facilities
is at high risk for infection with hepatitis viruses (both B and C), the modes of
disease transmission being already known.
PMID- 22046781
TI - Methods for estimating "dry weight" in hemodialysis patients.
AB - The correct estimation on dry weight is very important in providing effective and
safe hemodialysis to end stage renal disease patients. Optimal fluid removal with
minimal adverse reactions from the treatment is one goal of hemodialysis
treatment. The aim of this article is to discuss different methods of assessing
dry weight and to determine their role in the complex fluid management of end
stage renal disease patient. Recent literature describes various methods of
determining optimal hydration state, including clinical or paraclinical methods.
Each of these methods has their benefits and limitations. Despite the large
number of studies conducted on new technologies for determining dry weight, there
is a lack of larger, randomized controlled trials to support these methods.
Although the successful use of different methods of dry weight assessment is not
supported yet by large clinical trials, some evidence is starting to link the use
of some methods to improved outcomes (morbidity, mortality) in this population.
PMID- 22046782
TI - [Relevance of L-type calcium channels for the non-genomic effects of estradiol
and aldosterone upon contractile activity in isolated arteries].
AB - Non-genomic vascular effects of steroids are incompletely understood, despite
progress made regarding some aspects, such as the mechanism of endothelium
dependent relaxation by estrogens. AIM: To investigate the involvement of certain
mechanisms in the rapid, non-genomic effects of estradiol (EST) and aldosterone
(ALD) on endothelium-dependent and -independent vasomotor responses. MATERIAL AND
METHODS: Isometric myography of rings from aorta, mesenteric arch, and first
order mesenteric branches isolated from male Wistar rats was used. RESULTS: We
found that L-type calcium channels (Cav1.2) are important for endothelium
independent relaxation induced by EST, while ALD reduces the involvement of
Cav1.2 in phenylephrine-induced contraction and potentates both NO- and EDHF
mediated endothelium-dependent relaxation. To further examine the relevance of
Cav1.2 for the vascular effects of EST and ALD, we were using rings with and
without functional endothelium, precontracted by direct activation of Cav1.2 (Bay
K 8644), high extracellular K+, phenylephrine, and under complete Cav1.2 block
(nifedipine). Data suggest that EST, which directly inhibits Cav1.2 in
transfected HEK cells, uses mainly this path to induce endothelium-independent
relaxation, and that ALD may induce a rightward shift in the voltage-dependence
of Cav1.2.
PMID- 22046783
TI - [Improvement of genetic diagnostic strategy in velo-cardio-facial syndrome].
AB - Velo-Cardio-Facial Syndrome (VCFS) is characterized by congenital heart defects
(CHD), palatal abnormalities, facial dysmorphism, neonatal hypocalcemia, immune
deficit, speech and learning disabilities. SVCF is caused by microdeletion
22q11.2. Microdeletion is detected by fluorescence in situ hybridization (FISH).
The highly variable phenotype makes diagnosis and selection for FISH more
difficult. AIM: To retrospectively analyze and compare the phenotype of children
with a clinical diagnosis of VCFS with/without 22q11 deletion; to verify the
validity of literature guidelines and to describe combinations of clinical
features that should lead to molecular analysis. MATERIAL AND METHODS: The
present study was performed in 21 patients with a clinical diagnosis of VCFS.
Methaphase chromosome spreads were prepared from phytohaemagglutinin stimulated
lymphocyte culture by standard methods before FISH. The patients were divided
into two groups according to FISH test: positive and negative. RESULTS: The
features commonly noticed in FISH positive patients were: palatal
abnormalities/hypernasal speech, learning disabilities, facial dysmorphism,
tapered fingers (6/6), CHD (5/6) and recurrent infections (2/6). In FISH negative
patients the following were found: learning disabilities, CHD (12/15); facial
dysmorphism (10/15), family history of CHD (7/15), short stature (6/15),
hypocalcemia, tapered fingers (5/15), recurrent infections (3/15) and palatal
cleft (2/15). In both groups, Tobias and McDonald-McGinn guidelines were
positive. CONCLUSIONS: VCFS has a highly variable phenotype. Our study suggests
that 22q11.2 deletion analysis by FISH should be performed in patients who have
at least 2 (newborn)/3 (child, adult) specific criteria: CHD, hypocalcemia,
palatal abnormalities, facial dysmorphism, learning disabilities, digital
anomalies, and immune deficit.
PMID- 22046784
TI - [Descriptive assessments of a series of rheumatoid arthritis patients admitted to
rehabilitation treatment between 2008 and 2010].
AB - AIM: To assess some demographic features in a series of 741 rheumatoid arthritis
patients admitted to the Clinic Hospital of Rehabilitation at Iasi in different
stages of disease in order to select the most adequate rehabilitation teratment.
MATERIAL AND METHODS: Data were collected from patients' records, hospital
statistical reports, and then processed and interpreted using EPI/INFO and MS
Excel. RESULTS: Sex distribution revealed that the disease was more common in
females (male/female ratio 0.2). The prevalence was higher after the age of 40,
from 15.4% to 33.8% between 51 and 60, and 40.2% after 61. The most important
comorbidities were related to osteoporosis (48.9%), ischemic cardiopathy and
essential arterial hypertension (40.1%), impaired glucose tolerance and diabetes
mellitus (36.9%), viral hepatitis B and C (24.02% of all cases). CONCLUSIONS: In
selecting the most adequate rehabilitation treatment (drug therapy,
kinetotherapy, and physical therapy) patient's age, and his various associated
diseases have to be considered.
PMID- 22046786
TI - [Metabolic syndrome in HIV-infected patients with favorable response to
antiretroviral therapy].
AB - AIM: The assessment of the metabolic syndrome prevalence, as defined by the
American Heart Association/The US National Cholesterol Education Program Adult
Treatment Panel, (AHA/NCEP III updated), has been made in 68 polyexperimented HIV
infected patients that received antiretroviral therapy over 24 months and who
have a favorable viroimunologic response (undetectable plasmatic viral load).
MATERIALS AND METHODS: this cross-sectional analytical study has been carried out
on a cohort of 68 patients clinically and paraclinically monitored at the
HIV/AIDS Department. RESULTS: The response to antiretroviral therapy clinically
and paraclinically evaluated after two years from the initiation of the novel
HAART scheme has been favourable in all the 68 patients. Only 4 (0.58%) of the
patients fulfill the criteria of the metabolic sindrome definition. The
statistical analysis does not indicate an increase in the risk of the metabolic
syndrome development in these polyexperimented patients, where the clinical
symptoms connected with the lipodistrophic syndrome with lipoatrophy are
preponderent, associated with different types of antiretroviral drugs.
CONCLUSIONS: The metabolic syndrome criteria are not applicable in the case of
HIV infected patients (infected in the first year of life), polyexperimented at
HAART therapy with favourable viroimmunologic response.
PMID- 22046785
TI - [Aspects of the antimicrobial resistence profile in infections with Escherichia
coli and Klebsiella pneumoniae in diabetic patients].
AB - Infections in diabetic patient remains an important cause of morbidity and
mortality, triggering and maintaining a prolonged metabolic imbalance. Emergence
of extented spectrum beta-lactmase (ESBL) in Escherichia coli and Klebsiella
pneumoniae is a major concern, because of the atypical manner infection acts in
this group of imunodepressed patients and also for the limited therapeutic
solutions. For this reason we have evaluated the profile of antimicrobial
resistance of these pathogens in both diabetic and non diabetic patients.
MATERIAL AND METHOD: The aim of this study was to evaluate, in a retrospective
case control study, the antibiotic susceptibility pattern in isolates of E. coli
and Klebsiella spp. from different biological products in 49 diabetics and 150
non-diabetics admitted in The Clinical Hospital of Infectious Diseases Iasi over
a period of two years. RESULTS: Most of strains of E. coli and Klebsiella spp.
ESBL positive were found in uroculture. Significant differences in E. coli
resistance rate between diabetics and nondiabetics were noted for amoxicillin
clavulanic acid and ciprofloxacin (31,4% vs.13,98%, p=0,04, respectively 52,9%
vs. 24,46%, p=0,004). More isolates of ESBL positive K. pneumoniae were found in
diabetic patients (50% vs. 24%). Ciprofloxacin resistance of K. pneumoniae was
significantly higher in diabetics (75% vs 39%; p=0,05). There was no resistance
in E. coli and K. pneumoniae isolates to imipenem in the diabetic group.
CONCLUSIONS: The high resistance rate to quinolones and 3rd generation
cefalosporins limits their use for the treatment of Escherichia coli and K.
pneumoniae infections. Other alternatives for empiric therapy in community and
nosocomial-acquired infections in diabetic patient remains carbapenems,
aminoglycosides and colimycin.
PMID- 22046787
TI - Diagnostic approach of pneumonia in an elderly patient with comorbidities--case
report.
AB - Dyspnea is one of the symptoms that has a major impact on patients' health, with
a negative influence on the quality of life. The main causes of dyspnea are
cardiac, pulmonary and mixed (cardiac or pulmonary). There are several other
causes such as metabolic conditions (acidosis), pain, neuromuscular disorders,
otorhinolaryngeal disorders, anxiety, panic disorders and hyperventilation. Acute
pneumonia in the elderly is a common occurrence and its incidence grows as the
elderly population increases. We report the case of a 76 years old patient with a
known cardiovascular condition, recently hospitalized for right pulmonary
infarction. He presented to our clinic for influenced general state, rest
dyspnea, fever, shiver, and productive cough in the last two days. Current
medication included oral anticoagulants and triple antihypertensive treatment
(responsible for his low blood pressure). Laboratory results showed a nonspecific
inflammatory syndrome with leukocytosis and neutrophilia and mild normochromic
normocytic anemia; D-dimers were within normal range, fibrin degradation products
1+; myocardial enzyme testing showed no alteration, and BPN (beta natriuretic
peptide) was 790 pg/ml. Chest X-ray showed diffuse bilateral reticular shadows
(more pronounced on the right side) and left costodiafragmatic opacification. It
appears that age-related increase in morbidity and mortality in community
acquired pneumonia is not due to age per se, but to interactions between the
immune system, systemic diseases and nutritional factors. Community-acquired
pneumonia in the elderly is known to have a high mortality. Although the
diagnosis can be easy, the physician must also investigate for less obvious
causes of dyspnea such as the presence of comorbidities and fragility of the
elderly patient.
PMID- 22046788
TI - [Toxic cause febrile neutropenia].
AB - Agranulocytosis is an acute disease with severe leucopenia, especially with low
neutrophils, elements with an essential role in the organism's defense. It is
more frequent at adult age (between 30 to 70 years of age) especially in women.
We present the case of a 84 years old patient that, following passive exposure to
pesticides, develops a severe neutropenia with a fast response to the
administration of Methylprednisolone and granulocyte colony-stimulating factor (G
CSF-Filgrastim 48MIU/0.8mL/day, for three days). The diagnostic certainty was set
by the bone marrow puncture which excluded a possible aleukemic acute leukemia or
a myelodysplastic syndrome.
PMID- 22046789
TI - The prognosis of posterior urethral valves, associated to vesicoureteral reflux
in children.
AB - Posterior urethral valves represent a congenital barrier at the level of the
posterior urethra, which opposes miction. They are located near the prostatic
urethra, originating at the verumontanum level, affecting male patients. The
ureters are inconstantly dilated; vesicoureteral reflux is met in 2/3 of the
cases. The reflux can be secondary to the sub-bladder barrier, but it can also be
considered primitive, determined by the intra bladder ectopy of the ureter. The
presence of the reflux is interpreted as a severe associated factor. Semiology is
rather unusual, positive diagnosis is based on early discovery or antenatally of
the impairment, by fetal echography starting from the 28th week of pregnancy,
postnatal echography followed by miction cystography, retrograde urethrography
and creatinine dosage complete the diagnosis. The treatment is surgical:
endoscopic ablation of the valves (in the absence of renal failure), percutaneous
pyelostomy, high lateral ureterostomy, and in severe cases vesicostomy and renal
transplant. Prognosis depends on how early the impairment is detected, on the
degree of pulmonary hypoplasia, on the presence of the vesicoureteral reflux and
the possibility of recovering renal function; 1/3 of the newborns develop in time
Chronic Renal Failure which requires renal transplant. The studied group
comprised male children diagnosed with vesicoureteral reflux their ages ranking
between 0 -18 years, admitted to the Pediatric Clinic, Tg. Mures during the last
10 years and children diagnosed and operated with posterior urethra valves at the
Surgical Clinic of the "M. S. Curie" Hospital, Bucharest during the last 20
years. Our results show that out of the total number of studied children 25
presented posterior urethra valves and 9 children presented vesicoureteral
reflux. We can conclude that the presence of the vesicoureteral reflux is an
unfavorable prognosis regarding the degree of renal failure.
PMID- 22046790
TI - [Industrial sound spectrum entailing noise-induced occupational hearing loss in
Iasi industry].
AB - In European Union every day millions of employees are exposed to noise at work
and the risk this can entail. AIM: this study presents the sound spectrum in Iasi
heavy industry: metal foundries industry, punching and embossing of metal sheets,
cold and hot metal processing. MATERIAL AND METHODS: it was used a type 2 Sound
Level Meter (SLM) and the considered value was the average value over 10 test
values in 10 consecutive days for each octave band in common audible frequency
range. RESULTS AND DISCUSSIONS: It is obviously that the large values of sound
intensities in the most of frequency octave band exceed maximum admissible and
legal values. CONCLUSIONS: The study reveals the necessity of hardware, medical
and managerial measures in order to reduce the occupational noise and to prevent
the hearing acuity damage of the workers.
PMID- 22046791
TI - [Sinonasal headache--reality or mis-diagnosis?].
AB - Facial pain can be the presenting, and sometimes the only, complaint of many
disorders that originate from cranial structures. One causes of facial
pain/headache is sinusitis, in both its acute and its chronic presentation.
Successful management of headache is preceded by the identification of an
etiology and precise diagnosis. MATERIAL AND METHODS: A prospective study was
carried out on a series of 71 patients treated in the ENT Department of Iasi "Sf.
Spiridon" Hospital between January and august 2009 for pathology implying facial
pain, headache, facial pressure, nasal obstruction, rhinorrhea. The therapy was
medical and surgical and pursued nasal desobstruction, sinusal drainage and
ventilation. Data regarding different parameters were analyzed pre and post
therapy. RESULTS: After the proper treatment for each situation, the parameters
analyzed improved significantly, although, in some cases the main accuses
regarding the pain remained unchanged or slightly ameliorated. CONCLUSIONS:
Depending on the clinical suspicion of the possible etiologies of facial pain and
headache, the appropriate consultations should be made. For concerns of head and
neck lesions or sinus-related headache, an otolaryngologist should be consulted.
If a primary headache syndrome or a cranial neuralgia is of concern, the patient
should be evaluated by a neurologist. Dentists and oral surgeons should be
involved. In some cases, a psychiatry referral is appropriate. The surgical
treatment can be effective if the pathology meets the criteria of sinonasal
facial pain.
PMID- 22046792
TI - [Borderline ovarian tumors and global radiation in relation with climate change
impact].
AB - There is limited information on borderline ovarian tumor detected intra
surgically and its most favorable treatment in relation with global radiation and
climate changes. AIM: To study the pre-surgery and intra-surgery differentiation
criteria of borderline ovarian tumors from invasive carcinoma, and to make a very
complex analysis of the frequency, distribution, and variation in time of global
radiation, temperature, and precipitation in North-East Romania. MATERIAL AND
METHOD: The 54 patients (age range 20-78 years, mean age 46 years) included in
this study had borderline ovarian tumors surgically treated during the last 22
years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iasi, and
representing 4.87% of the total 1107 ovarian tumors detected and treated during
this interval. The histological types were: serous (18 cases), mucinous (27
cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the
impact of climate changes on borderline ovarian tumors a thorough study on the
frequency of global radiation in relation with climate changes based on data
recorded in the last 55 years was also carried out. RESULTS: The distribution of
these cases depending on when surgery was performed was analyzed. In our study
the frequency of ovarian borderline tumors (4.87%) is lower than in similar
reports in the literature being due, in our opinion, to the influence of global
radiation in relation with climate changes. CONCLUSIONS: In our study global
radiation is probably responsible for a progression to invasive carcinoma in 0.7%
of the borderline ovarian tumors.
PMID- 22046793
TI - [Parapharyngeal space--history and surgical study].
AB - One area of anatomy, which is a true passage of secrecy, is the anatomy of the
potential anatomical spaces. The study of the fascial layers of the head and neck
and the potential spaces they make-up is both fascinating and confusing. Much of
the confusion is a function of the multiple synonymous terms and classifications
that various authors use, and not the basic anatomical description. Their anatomy
and communications, to the base of skull and downward to diaphragm, acts like a
route through which infection from mouth and throat can reach the superior
mediastinum. CONCLUSIONS: Understanding the anatomy of the parapharyngeal space
is important in making a correct diagnosis and surgical plan for removing tumors
in this region.
PMID- 22046794
TI - [Binaural cochlear implant--good choice in the treatment of deep sensorinural
hearing loss].
AB - Nowadays. cochelar implant is the only choice of treatment in deep bilateral
deafness. AIM: To evaluate the benefits of binaural implantation of a single
receiver-stimulator device by using audiometric tests at 3 and 6 months
intervals. MATERIAL AND METHODS: The study included 3 patients with bilateral
sensorineural deafness of cochlear origin. Following implantation they were
assessed by pure tone audiometry (PTA), speech audiometry (SA), and sound
localization tests (LT). RESULTS: PTA showed a significant decrease in hearing
thresholds level during the 6-month interval following implantation. As to the
degree of speech discrimination in both quiet and noisy environment, SA showed
evident progress at 6 months compared to the results at 3 month. The location
tests revealed improved sound localization in both ears at 6 months compared to
the results at 3 months. CONCLUSIONS: Compared to unilateral implant, the
binaural cochlear implant has the advantage of stereophonic hearing, facilitating
the communication through a better understanding of speech in both quiet and
noisy environment, and improving the quality of life by the location of sounds
similar to natural hearing.
PMID- 22046795
TI - [Expression of hormonal receptors (alpha-estrogen, beta-estrogen, progesteron),
Ki-67 and P53 in endometrium of tamoxifen treated breast cancer patients].
AB - Tamoxifen is the most commonly prescribed adjuvant therapy for women with breast
carcinoma ER+. It has agonist activity on the endometrium and is associated with
an increased risk of endometrial carcinoma. The aim of this study was to evaluate
the immunohistochemical changes on the histological endometrial modification from
the patients treated with tamoxifen. MATERIAL AND METHOD: A group of 20 women
selected from 125 patients with breast carcinoma, with adjuvant therapy. The
criteria of selection were the histopathological proliferative changes of
endometrium from these symptomatic patients. The 20 specimens of endometrium were
evaluate immunohistochemycal by estrogen receptor alpha, beta, progesterone
receptor, Ki-67 and P53. RESULTS AND CONCLUSIONS: The 20 endometrium specimen
showed histological proliferative endometrial lessions, including polyps,
hyperplasia and carcinoma. Immunohistochemical, benign lessions showned
expression of estrogen alpha and beta receptor, low expression Ki-67 and absent
expression of P53. These tests were negative in clear cell carcinoma, but were
intens positive for Ki-67 and P53. In general, tamoxifen associated endometrial
adenocarcinoma were characterized by a lower expression of estrogen receptor
alpha, higher expression of progesterone receptor, and more frequent expression
of estrogen receptor beta than endometrial spontaneous tumors.
PMID- 22046796
TI - [The lymph nodes status--prognostic factor in breast cancer].
AB - AIM: The assessment of the survival rate according to axillary lymph nodes status
in patients diagnosed with breast cancer. MATERIAL AND METHODS: The study group
included 206 women, treated in the 4th Obstetrics and Gynecology Clinic during
2002-2005. All patients were treated surgically with lymph nodes dissection. The
analyzed variables included clinical and morphological features of both primary
tumor and axillary lymph nodes. We have evaluated 5 years survival in relation to
positivity and number of dissected lymph nodes. In order to determine the
prognostic value of evaluated variables we have used Kaplan Meir method. RESULTS:
77.7% of all patients were aged between 40 and 49 years old and 62.6% of them
presented stage II tumors. Invasive ductal carcinoma was the most frequent
histologic type (79.12%) and 71.2% of tumors were moderated of poorly
differentiated, lymph nodes invasion being presented in 93 cases. Survival was
significantly influenced by lymph node status (p = 0.0001), number of involved
nodes (p = 0.0001), number of dissected nodes in pN0 patients (p = 0.0001) and
application of adjuvant systemic therapy in pN0 patients (p = 0.0001).
CONCLUSIONS: The pathological examination of axillary nodes in breast cancer
patients offers a valuable information regarding survival. The absence of lymph
node metastases of 10 lymph nodes dissection or more, and the application of
adjuvant systemic therapy favorably influence the survival.
PMID- 22046797
TI - [Incidence of congenital malformations in the Iasi "Cuza Voda" Maternity
Hospital].
AB - AIM: To update the data on the incidence of congenital malformations in our area
and emphasize the importance of prenatal diagnosis. MATERIAL AND METHODS: The
study was conducted over a period of ten years and included 2211 cases with
congenital malformations. Such parameters as the incidence of malformations over
these years, gestational age at the moment of diagnosis, and mortality from
congenital malformations were followed. Statistical and graphical data were
processed with the help of SPSS 16.0 and MS Excel software. RESULTS: The total
prevalence of malformations was 3.52%, comparable with the data in the
literature. Over this period a number of 262 cases (11.8%) ended in spontaneous
miscarriage or termination of pregnancy for fetal abnormalities. A significant
percentage of these pregnant women gave birth to their child, many of them dying
shortafter. CONCLUSIONS: Congenital malformations remain the leading cause of
mortality in neonates. In Romania, the advanced techniques of prenatal diagnosis
being used only in specialized centers, and a large number of cases may escape
early diagnosis. This study underlines the importance of a correct assessment of
fetuses so that the discovery of fetal abnormalities at birth not to be a
surprise.
PMID- 22046798
TI - [Functional reeducation of flexor tendons with associated lesions in zone II-
comparative study].
AB - Regaining satisfactory digital function after flexor tendon laceration and repair
has long been one of the most important problems in hand surgery. But optimal
therapy is often difficult to ascertain, given the plethora of immediat
postoperative protocols published in the scientific literature. AIM: The purpose
of this study is to compare the functional results between Kleinert,
Silfverkiold, Gratton and Strickland protocol towards evaluate them by
interconnection and with the literature. MATERIAL AND METHODS: The prospective
study enorolled 75 patients who presented in our cabinet consecutives during
1.05.2008-1.12.2010. The subjects were evaluated regarding Total active motion
test and Grip strenght test at 12 weeks postoperative. RESULTS: We found the best
results to Gratton group, followed by Strickland, Silfverkiold-May and Kleinert
groups. CONCLUSIONS: We conclude that, for the tendinous lessions with associated
injury (nervs and vessels) in zone II, our first therapeutical indication is to
use the Gratton protocol.
PMID- 22046799
TI - [Rare clinical situatons of the diverticuli of the colon].
AB - It is well known that the diverticuli of the colon gets inflamed in 10-15% of
cases, thus becoming clinical symptomatic as a diverticulitis, while in other 15%
they will bleed, with the clinical aspect of an inferior digestive bleeding. Our
study presents some clinical observations with diverticuli of the colon, that
raised diagnostic and therapeutic problems. MATERIAL AND METHOD: Between 2001
2010, 17 patients were admitted in the 3rd Surgery Clinic, University Hospital
"St.Spiridon", Iasi, with asymptomatic diverticuli of the colon, that were put in
evidence imagistically, intraoperative or on specimens after removal of the colon
for other conditions;meanwhile, there were 15 patients admitted with
complications of the diverticuli:5 patients had perforated diverticulitis (4
pericolic abscesses and one with peritonitis in the lower abdomen), 4 had rectal
bleeding and the other 6 raised particular problems of diagnostic and treatment,
being included in the present study. RESULTS: Five out of six underwent
operation. One patient refused the surgical treatment. Postoperative evolution
was favorable in 4 out of the 5 operated patients. CONCLUSIONS: The complications
of colonic diverticuli present on admission under clinical aspects that usually
mimic a colonic cancer. In these situations the imagistic examinations do not
offer enough details to elucidate the diagnosis. Our six particular observations
strengthen the dictum of avoiding the "mirage" of the first lesion. The extent of
the surgical procedure in the case of patients with colonic diverticuli admitted
under the clinical aspect of a complication is sometimes disproportionate and
encumbered of increased mortality and complication rate.
PMID- 22046800
TI - Biocompatibility testing of chitosan hydrogels.
AB - Chitosan is a linear, natural cationic polysaccharide comprising beta-1,4 linked
glucosamine and N-acetyl-D-glucosamine. Hydrogels of chitosan were prepared by
crosslinking with varying amounts of glutaraldehyde. It can be used as a
bacteriostatic, fungistatic and coating agent, and the gels and suspensions may
play the role of carriers for slow release or controlled delivery of drugs, as an
immobilizing medium and an encapsulation material. MATERIAL AND METHODS: Chitosan
and glutaraldehyde were used to prepare the hydrogels and their characteristics
were investigated by Fourier transform infrared (FT-IR) spectroscopy and the
inhibitory effect on cellular growth was tested by chemiluminescence assay. The
hemolytic activity was also determined by direct contact with human blood and the
concentration of hemoglobin was spectrophotometrically measured. RESULTS AND
DISCUSSION: Chitosan hydrogels have no inhibitory effect on cell growth, and
hemolytic action below 1%, which means good blood compatibility; therefore they
are promising materials.
PMID- 22046801
TI - [The influence of stress factors on liver function and lipid metabolism in an
animal model of arterial hypertension].
AB - AIM: to investigate the influence of some stress factors on hepatic function and
lipid metabolism in an experimental-induced hypertension. MATERIAL AND METHODS:
The experiment was carried out on Wistar rats, treated intraperitoneally, for 4
weeks, as follows: Group 1: saline solution (0.5ml/100g weight); Group 2: saline
solution + stress; Group 3: Endotelin-1; Group 4: Endotelin-1 + stress; Group 5:
Endotelin-1 + cholesterol diet (0.2g/kbw/day); Group 6: Endotelin-1 + cholesterol
diet + stress. Endotelin-1 0.25nmol/kbw was initially administered, followed by
0.5nmol/kbw 15 min later, 2 times/week. Stress-inducing factors were
immobilization and water immersion. In the 28th day of the experiment blood
pressure was measured and blood samples were taken from retro-orbitary plexus to
assess glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase
(GPT) and lactic dehydrogenase (LDH) activity, total cholesterol, low-density
lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol,
triglycerides levels. RESULTS: Using immobilization and water immersion as
chronic stress, our study proved an increase of GOT, GTP and total and LDL
cholesterol in rats with endotelin-1-induced hypertension. CONCLUSIONS: In this
animal model of endothelin-1-induced hypertension the blood pressure increased
significantly under chronic exposure to stress, reaching the highest values when
associating stress and experimentally induced dyslipidemia.
PMID- 22046802
TI - [Experimental research regarding the influence of the stress factors in an animal
model of HELLP syndrome].
AB - AIM: to study the effects of licht/dark induced-stress in an animal model of
HELLP syndrome. MATERIAL AND METHODS: The experiment was carried out on white
female Wistar rats treated intraperitoneally, for 4 weeks, as follows: Group 1:
saline solution 0.5ml/100g weight; Group 2: saline solution + dark induced
stress, continuously, 28 days; Group 3: saline solution + light induced-stress,
continuously, 28 days; Group 4: endotelin-l; Group 5: endotelin-1 + dark induced
stress, continuously, 28 days; Group 6: endotelin-1 + light induced-stress,
continuously, 28 days. Endotelin-1 0.125nmol/kbw was initially administered,
followed by 0.25nmol/kbw 30 min later, 2 times/week. RESULTS: At the end of the
experiment blood pressure was measured and blood samples were taken to assess:
leukocyte formula, phagocytic capacity of peripheral neutrophils and serum
complement activity, aspartate aminotransferase (ASAT), alanine aminotransferase
(ALAT) and lactic dehydrogenase (LDH) activity, total bilirubin and lipid
profile. CONCLUSIONS: In these experimental conditions we obtained an animal
model of partial HELLP syndrome (elevated liver enzyme levels and a low platelet
count, values emphasized by light induced-stress, without hemolysis). In
chronically stressed animals we found the highest levels of blood pressure, a
decrease of plasmatic cortisol level and of phagocytic capacity of peripheral
neutrophils and an increase of total cholesterol.
PMID- 22046803
TI - [Assessment of some biophysical parameters of human erythrocyte by FT-IR
spectroscopy--preliminary study].
AB - Based on the biochemical composition of erythrocyte membrane and asymmetric
distribution of phospholipids, proteins, and cholesterol, FT-IR spectroscopy can
monitor the distribution and interaction pattern of membrane constituents.
MATERIAL AND METHODS: The study series included 21 clinically healthy subjects
aged between 20 and 60 years. Complete blood counts were performed and the serum
biochemical compounds (cholesterol, triglycerides, total protein, glucose) were
determined. RESULTS AND DISCUSSIONS: The parameters that can be assessed by
erythrocyte FT-IR in relation with the biochemical factors that may influence
membrane fluidity are: degree of fatty acids unsaturation, saturated fatty
acids/unsaturated fatty acids ratio, cholesterol/phospholipids ratio, and
phospholipids/protein ratio. Based on the obtained results, in the assessment of
membrane status the following vibration modes were selected as spectral
parameters: vibration associated valence bond (=CH), asymmetric valence CH2
groups, modes associated with P=O bond and amine bands I and II specific for
proteins. Other parameters, such as v(C-O) specific to glucose, may provide
additional information on glucose metabolic status. CONCLUSIONS: By correlating
biochemical markers with these spectral parameters information on red cell
membrane status, status that may reflect different pathological processes, can be
obtained.
PMID- 22046804
TI - [Contributions to the assessment of hemodynamic status in metabolic syndrome].
AB - The concept of normohemodynamics is based on the fact that the main function of
the cardiovascular system is the transport of oxygen. The cardiovascular system
is adapting to a new hemodynamic status with every heartbeat. Only one class,
called the normohemodynamic state, containing a simultaneous normotension and
normodynamic flow, can serve as therapeutic goal. Metabolic syndrome includes a
constellation of clinical and biological features that confer an increased
cardiovascular risk. Clutter hemodynamic modulators in metabolic syndrome and
assessment of hemodynamic status both overall and by its components, open new
perspectives in the management of patients with hypertension and metabolic
syndrome. MATERIAL AND METHODS: In the current study were included 32 patients
meeting the criteria for metabolic syndrome and hypertension and 32 controls.
Patients were monitored and assessed for the global hemodynamic status and for
the modulators of hemodynamics, intravascular volume, vasoactivity and inotropy,
respectively. RESULTS AND CONCLUSIONS: There are no significant differences in
the global hemodynamic status between the study group and the control group; in
the study group there is a clear weathering of hemodynamic modulators. The
improvement of these factors opens a new perspective in the global cardiovascular
assessment and therapeutic directions.
PMID- 22046805
TI - [Morphopathological changes in glaucoma-induced trabecular meshwork].
AB - Glaucoma causes trabecular meshwork and Schlemm canal changes, resulting in the
obstruction of the aqueous flow at this level. AIM: To show the histological
changes in the surgically removed trabecular meshwork tissues. MATERIAL AND
METHOD: Trabecular meshwork fragments were histologically processed for
histological diagnosis. RESULTS: 29.87% of all patients had ordered structure
with high eosinophilia, 20.12% a rare structure with high eosinophilia, 21.34% a
voluminous trabecular meshwork with fusiform cells, 21.03% tissue fibrosis and
7.62% had tissue necrosis. CONCLUSIONS: Aqueous flow obstruction in trabecular
meshwork is produced by the histological changes at this level, found in all
tissue specimens removed during surgery.
PMID- 22046806
TI - [Experimental research on the effects of a Cetraria islandica extract on
oxidative stress in laboratory animals].
AB - AIM: Experimental researches on the effects of a Cetraria islandica extract, with
or without magnesium association, on oxidative stress in rats. MATERIAL AND
METHODS: The experiments were carried out on Wistar rats, treated
intraperitoneally for 14 days at single daily dose as follows: Group 1: Saline
solution (SS) (0.5 ml/100g bw/day); Group 2: Subcutaneous pellets, SS; Group 3:
Levamisole (LEV) (10mg/kbw/day); Group 4: Subcutaneous pellets, LEV; Group 5:
Prednison (PDN) (5mg/kbw/day); Group 6: Subcutaneous pellets, PDN; Group 7: MgSO4
(5mg/kbw/day); Group 8: Subcutaneous pellets, MgSO4; Group 9: C. islandica (Ci)
extract (21.56mg/kbw/day); Group 10: Subcutaneous pellets, Ci; Group 11:
Ci+MgSO4; Group 12: Subcutaneous pellets, Ci+MgSO4. At the end of the experiment
blood samples were collected for assessing the following oxidative stress
parameters: malonaldehyde, catalase, glutathione peroxidase, glutathione levels.
RESULTS: In the rats with or without experimentally-induced granuloma, repeated
administration of Ci for 14 days resulted in a decrease of malonaldehyde,
catalase, glutathione peroxidase activity, and an increase in glutathione levels.
The association of magnesium augmented the antioxidant effect of Ci in this
experimental model. CONCLUSIONS: In our study experimental conditions C.
islandica extract determined adaptogenic-antistress effects, confirmed by its
actions on oxidative stress parameters.
PMID- 22046807
TI - [Epidemiological observations on survival in the first year after acute ST
elevation myocardial infarction (STEMI) treated by primary angioplasty].
AB - Conditional analysis of survival factors after acute myocardial infarction is
important in care practice. We analyzed the survival and occurrence of coronary
ischemic events during the first year after the episode of acute myocardial
infarction with ST segment elevation (STEMI). We prospectively evaluated at one
month and one year the patients with STEMI assisted in November 2008 - February
2010 at Heart Institute "Niculae Stancioiu" with primary coronary angioplasty
(ACP) performed during the first 12 hours of the onset of pain. We analyzed
statistically survival and occurrence of ischemic events. Survival rate was 95.6%
(CI95%: 92.7 to 97.3) at one month and 92.1% (CI95%: 87.8 to 94.2) ate one year
after STEMI. Survival was significantly reduced in anterior STEMI (83.4%),
history of ischemic heart disease (83.4%), stroke (81.2%), females (81.8%) and
ischemia exceeding > 6 hours (83.6%). The rate of ischemic events avoidance was
96.5% (CI95%: 0.938 to 0.980) at one month and 81.7% (CI95%: 76.7 to 85.6) at one
year after STEMI. The ischemic events, as evaluated through avoidance rate of
phenomena, were significantly more frequent in females (69.9%), dyslipidemic
(72.9%), hypertensive (73.7%) patients, having history of ischemic heart disease
(72.4%) and total ischemia time longer than 6 hours (70%). Evolution of patients
with STEMI after ACP is significantly better in patients with non-anterior
location, males, without history of coronary disease, stroke, hypertension,
dyslipidemia, ischemic time > 6 hours.
PMID- 22046808
TI - [Clinical epidemiological study of acute gastro-enteritis outbreak recorded in a
children community, in Iasi, May, 2009].
AB - Acute diarrheal disease affect all demographic structures and it is considered a
major cause of morbidity and mortality for young age groups; underreporting is
due to clinical and epidemiological diversity, everywhere, including the
developed countries. MATERIAL AND METHODS: The authors present an epidemic
outbreak of acute gastroenteritis by rotavirus in a community of 240 children.
Processing and interpretation of collected data was done by statistical,
mathematical and computerized methods. RESULTS: A number of 17 cases of acute
gastroenteritis caused by rotaviruses were detected and confirmed, mostly in
children older than 5 years (92%), with a tendency to focus on large group "A",
40%. All cases showed mild forms evolving medium. CONCLUSIONS: The 17 cases of
infection with rotaviruses were the second episode of acute gastroenteritis with
the same etiology, reported over two months. Extensivity of the epidemic outbreak
was moderate, with the predominant age group affected over six years (58%).
Developing and implementing preventive measures included daily cleaning and
decontamination standards.
PMID- 22046809
TI - [Study about the associated use of different types of drugs by high school
students].
AB - Socially acceptable drugs and illegal substances consumed by high school students
affect their nervous system, which is under development and anticipate an
extensive drug use later. MATERIAL AND METHOD: In our study we have assessed the
associate drug consumption at a group of high school teenagers by applying a
questionnaire with 23 items. RESULTS AND DISCUSSION: Tobacco use is the lowest in
ninth grade students and it is significantly better represented in higher grade
students. Regardless of the grade, there are no significant differences in the
proportion of boys and girls who smoke, even the health risks posed by smoking
are known to over 80% of respondents. Among the reasons that could cause the
student smoking cessation predominates, at the smallest students, parents' threat
(significantly stronger than at those of senior grades), unlike the senior
students, which give a higher value to a possible alteration of their own health
status. The temptation for beer consumption appears before the age of 11 years
and it is mentioned about a quarter of all respondents. Drinking a glass of wine
for the first time is placed around the age of 14 years for boys and 15 years for
girls. Marijuana is the drug exclusively consumed in the ninth grade and holds
supremacy and other classes. Barbiturates and amphetamines are known about two
thirds of the surveyed students. Risks involved by the association of alcohol
consumption, tobacco and drugs are represented differently in this group of
adolescents, and evolve differently as the students grow, mature and evolve, in a
positive manner for their existence or not. CONCLUSIONS: during the high school
years teenagers are tempted to diversify their drug consumption and to associate
them, even they know very well how serious are the health consequences of this
attitude.
PMID- 22046810
TI - [Use of real time PCR for testing Staphylococcus aureus isolates from the Iasi
Infectious Diseases Hospital].
AB - S. aureus is capable of producing a wide spectrum of diseases and can quickly
develop resistance to antibiotics. These features require a careful monitoring of
these organisms, by detection of resistance genes and virulence factors, such as
Panton-Valentine leukocidin (PVL). AIM: To determine the presence of mecA and pvl
genes in S. aureus isolates by a Real Time-PCR technique (RT-PCR) in order to
shorten the detection time. MATERIALS AND METHODS: We tested 119 strains isolated
from pus, using phenotypic methods for methicillin resistance characterization,
according to CLSI 2008-2010 guidelines. Detection of mecA and pvl genes was done
with hydrolysis probes. RESULTS: The prevalence rate of methicilin resistant S.
aureus (MRSA) was 40,33%, and pvl was detected in 52,08% of those strains. The
results of the conventional methods for methicillin resistance detection were
validated by those obtained by RT-PCR CONCLUSIONS: RT-PCR is useful in
epidemiological surveillance of MRSA and PVL-producing strains and validation of
test results for phenotypic resistance to oxacillin.
PMID- 22046811
TI - [Assessment of the congenital syphilis prevention programs].
AB - The Romanian program for the management and screening of syphilis includes the
recording, follow-up, and antenatal care of pregnant women. It aims at testing
all pregnant women for syphilis with the help of VDLR (Venereal Disease Research
Laboratory) or RPR (Rapid Plasma Reagin) tests, and in the women with positive
tests to confirm the results by treponemal tests (treponemal antibodies): THPA
(Treponema Pallidum Hemagglutination), FTA-Abs (Fluorescent Treponemal Antibody
with Absorption), ELISA-Captia-IgM, and Western Blotting-IgM. In the pregnant
women with positive tests two doses of 2.4 million units of penicillin G
benzathine were administered at 5 days interval. These pregnant women are in the
evidence of a specialist (obstetrician, dermatologist), and District Department
of Public Health, and required to come for another serology test in 3 months. In
case they still test positive, the same treatment is applied at the beginning of
the third trimester of pregnancy. AIM: To assess the outcome of congenital
syphilis prevention programs in lasi, Romania. MATERIAL AND METHODS: In the
interval 2005-2011, in the Iasi town, 84 RPR positive pregnant women were
recorded. There was no significant difference in the number of pregnant women
residing in urban as compared to rural areas. Most of these women were from poor
social environments and had a low level of education. The diagnosis of acquired
syphilis was made by serological tests as most pregnant women presented in the
period of syphilis latency, being asymptomatic. All pregnant women followed the
treatment, and were tested periodically. Ultrasound examination was normal in all
women (no changes suggestive of fetal malformations). RESULTS: Free clinical,
laboratory, and ultrasound investigations, history taking, psychological
assessment, sex education, rapid identification of contacts of known patients,
follow-up of the interaction between health care providers and syphilitic
pregnant women, booklets, and leaflets altogether made that in the last 3 years
(2008-2010) no new case of congenital syphilis to be reported in the study area.
CONCLUSIONS: Encouraging women to attend antenatal care early in their pregnancy
is essential, this way all pregnancy-related problems (syphilis included) could
be managed.
PMID- 22046812
TI - [Dental treatment strategies for elderly patients].
AB - The elderly are influenced from a various and complex combination of factors,
such us individual genetic predispositions, lifestyle, society and environment,
the sum of all the individual life experiences concerning the dental care, the
caries, the periodontal and iatrogenic diseases. AIM: This paper evaluates the
dental treatment in the elderly. MATERIAL AND METHODS: The study was performed on
112 patients, aged over 65, at the Clinical Department of Dental Semiology und
Geriatric Dentistry, Iasi, Romania. RESULTS: The treatment interventions were
dental hygiene procedures (in 97 patients), restaurations (in 29 patients),
removable partial and total denture preocedures (in 50 patients), fixed
prosthetic procedures (in 18 patients), rebasing of dentures (in 25 patients) and
teeth extractions (in 26 patients). There were 36 endodontic emergencies and 15
periodontal emergencies and 8 emergencies that resulted from other causes.
CONCLUSIONS: The periodical dental examinations and the proper daily oral hygiene
routine are still important in the old age and they should not be neglected,
because the prosthetical components request also treatment interventions.
PMID- 22046813
TI - Endodontic retreatment in case of failure. Case report.
AB - In medical practice, clinicians come across an increased number of endodontic
treatments, which, like other dental treatments, can fail. The increase in the
number of endodontic treatment resulted in an increased number of failures, their
management raising complex and serious endodontic problems. The endodontic
retreatment of a failure is required by the increased desire to preserve the
tooth on the dental arch, thus preventing the need for dental extraction that may
have adverse consequences in terms of functional and psychological effect on
patients. This article presents two clinical cases that required endodontic
retreatment in order to avoid the complications that could ultimately require
tooth extraction. The teeth in question (a mandibular first molar and an upper
central incisor) having a special importance, and a physiognomic role, the
endodontic retreatment consisted in covering them in porcelain fused to the metal
crowns.
PMID- 22046814
TI - Pharmacokinetic modeling of glimepiride plasma concentration in healthy subjects.
AB - AIM: To determine the pharmacokinetics of glimepiride, a sulfonylurea
antidiabetic agent, after single dose administration in healthy subjects.
MATERIAL AND METHODS: Pharmacokinetic data for modeling were extracted from a
single-center, randomized, single-dose, fasting state, two-way crossover
bioequivalence study on 4 mg glimepiride in 24 healthy subjects. RESULTS: Plasma
concentrations of glimepiride were measured using a validated LC/MS/MS method.
The pharmacokinetic parameters were calculated using non-compartmental analysis.
Different pharmacokinetic models were tested to evaluate pharmacokinetics of
glimepiride. The optimal model was chosen based on Akaike's Information Criteria.
CONCLUSION: Compartmental analysis demonstrated that oral glimepiride tablets
obey one compartment open model with rapid absorption following a first order
kinetics and a short half-life.
PMID- 22046815
TI - [Interactions between oral anticoagulants and other medication in emergency
department--a pharmacoepidemiologic approach].
AB - Oral anticoagulants (OAC) are commonly used as a life-long therapy in the
prevention of systemic embolism in patients with atrial fibrillation, valvular
heart disease, prosthetic heart valves, and in the primary and secondary
prevention of venous thromboembolism, in patients with acute myocardial
infarction and angina pectoris. Drugs, herbs, and multivitamin supplements can
alter the absorption, pharmacokinetics or pharmacodynamics of OAC. AIM: To
investigate the possible interactions between oral anticoagulants and different
drugs administered in patients in emergency department. METHODS: This 1-year
exploratory investigation on 93 patients on OAC (aged 30 - 85 years), admitted at
two emergency departments of the Iasi "Sf. Spiridon" Hospital and Piatra Neamt
Hospital, consisted in their medical records analysis: diagnosis, recommended
treatement. Data were scored and statistically analyzed by t-test (Windows
Excel). The experimental protocol was in agreement with the recommendations of
the Gr.T. Popa University Committee for Research and Ethical Issues. RESULTS AND
CONCLUSIONS: Analysis and statistical processing of data shows that during the
study period 56 patients which received oral anticoagulant therapy associated
with different other medication belonged to the 60 and 80 years age group. This
finding suggests that the pathology is represented especially by atrial
fibrillation and myocardial infarction. The correlation between the therapy
consisting in OAC and sartan or nonsteroidal anti-inflammatory drugs and
International Normalized Ratio (INR), revealed a high level of anticoagulation
and an increase in hemorragic complications.
PMID- 22046816
TI - [Semi-quantitative determination of methadone by TLC].
AB - Methadone is the main therapeutic option in heroin addiction treatment, but also
an abuse substance. Given the analytical focus on the diagnosis of drug abuse and
the usefulness of toxicological analysis methods in both overdose and monitoring
substitution therapy, this study was aimed at the semi-quantitative determination
of methadone by using Thin Layer Chromatography (TLC). By having the advantage of
simplicity and rapidity, TLC finds its rightful place among the analysis methods
when other relatively costly methods that involve instrumental performance are
not available. MATERIALS AND METHODS: TLC plates (silicagel GF 254 Merck),
developing system methanol: strong ammonia 100: 1,5, photometric quantification
at 254 nm, using TLC Scanner 3 (Camag). RESULTS: The results show that methadone
can be determined semi-quantitatively in the chromatographic conditions mentioned
in the two domains tested (5 - 40 microg and 10 - 80 microg), with the best
results obtained in the 5 - 40 microg domain. CONCLUSIONS: Semi-quantitative TLC
evaluation proposed by us has as main advantages the rapidity, simplicity and
relatively low cost compared to other useful methods.
PMID- 22046817
TI - [Antimicrobial activity of some cinnamic acid derivatives].
AB - Due to drug-resistance phenomenon, there is a constant need for discovering new
antiinfectious agents. A series of cinnamic acid derivatives was synthesized and
then brominated with bromine in the presence of chloroform or acetic acid. The
structure of the new compounds was confirmed by elemental and spectral data.
Their antimicrobial activity was tested by disc-diffusion method. The tested
compounds had mainly antifungal activity and were moderately active against Gram
positive bacteria. Bromination of the double bond determined the enhancement of
the antimicrobial activity for all the tested compounds.
PMID- 22046818
TI - [Research for the improvement of acylation conditions in antistaphylococcal
penicillin synthesis].
AB - AIM: The 6-aminopenicillanic acid acylation with certain acyl chlorides was
performed in order to obtain antistaphylococcal penicillins with bigger crystals,
easy to filtrate (shorter filtration time), much pure, and an increased output.
MATERIAL AND METHODS: Oxacillin sodium salt was synthesized by acylating an
aqueous solution of 6-aminopenicillanic acid sodium salt (NaHCO3 not in excess)
with an ethylacetate solution of 5-phenyl-3-methyl-isoxazolyl-4-carboxilic acid
chloride. The crystallization was performed with a 40.5% sodium 2-ethyl hexanoate
izopropanolic solution. All tests (IR spectrum, iodometric titration, and
microbiological dosage) were performed according to the Xth Romanian
Pharmacopoeia standards. RESULTS: The amount of synthesized oxacillin was higher
and the output of 88,21%. Oxacillin had a high chemical purity (98,72%), and a
very good microbiological activity (95% of the standard activity). CONCLUSIONS:
Oxacillin crystals were bigger, the filtration speed was increased, and process
efficacy improved. The output of the process was also improved being higher than
with classical acylation.
PMID- 22046819
TI - [Comparative study of some clinical and laboratory indicators in a group of
patients using wells as source of drinking water and a control group using safe
water].
AB - In time, well water, as a source of drinking and coking water, with physical
chemical, bacteriological, and biological indicators suggestive of alteration in
water potability, determines complex, sometimes irreversible, metabolic
disorders. MATERIAL AND METHODS: Sixty individuals residing in a rural community
were divided into 2 groups: study group -30 subjects using well water, and
control group--30 subjects using safe water. For the study group the selection
criteria were: age, sex, use of well water as drinking and cooking water, history
suggestive of chronic poisoning (pregnancy course, birth weight, susceptibility
to infectious agents, and current chronic diseases). RESULTS: In the study group,
gestosis, prematurity, and altered body mass index are more frequent as compared
to the subjects in the control group. The identified laboratory changes indicate
moderate anemia, hepatic cytolysis, dyslipidemia, presence of nitrites in urine,
and positive urine cultures. CONCLUSIONS: Long-term use of water with mineral
constituents in excess, absent, or inadequate, the direct biological and chemical
water pollution, or most frequently the indirect pollution through the soil
determine, in time, complex, sometimes irreversible, metabolic disorders.
PMID- 22046820
TI - [The use of vascular prothesis Gore Viabahn in the managment of the lower limbs
ischemia].
AB - The chronic lower limbs ischaemia is caused mainly by arteriosclerosis. After
insufficient conservative treatment only the surgical intervention can salvage
the limb. The revascularisation surgery can be performed by open surgery with
implantation of the prosthetic bypass or by endovascular angioplasty with stent.
This second method seems to be the best alternative for the patients with several
concomitant systemic diseases. Nevertheless it is limited by presence of the long
distance arteriosclerotic lesions. The resolve of that problem is use of new
generation of long endovascular covered stents. They can be succesfuly used in
aorto-femoral and femoro-popliteal segment. Their efficiacy is simmilar to
traditional prosthetic grafts.
PMID- 22046821
TI - [The operations of the abdominal hernias with the use propylene material in
patients operated due to abdominal aortic aneurysm].
AB - The correlation between abdominal hernias and aortic aneurysm has been well
documented in literature. The pathophysiology of aneurysm and hernia formation is
seen within the abnormal collagen metabolism, resulting in extracellular matrix
defects. This study presents a group of 8 men in the age of 36 to 78 years old
(average 63, 5 years old) who underwent both an operation for the aneurysm and
for the abdominal hernia. Of the reported 8 patients, 7 had postoperative
hernias, where 4 of the cases there were recurrent postoperative hernias. The
remaining patient had an inguinal hernia. In 7 cases patients underwent an
abdominal aortic aneurysm (AAA) operation and in one case a hepatic artery
aneurysm endovascular operation was performed. Due to the fact that postoperative
hernias are an immense problem, especially within the group of patient with
collagen defects, the area of research and improvement of the materials that are
used in prosthetic hernia surgery today needs to progress. This study also
presents a short review of the various types of prosthetic materials used in the
production of hernial meshes. This is to emphasize the necessity of improving
operational techniques to minimize the risk of herniation, especially within a
group of patients with collagen defects.
PMID- 22046822
TI - [Use of synthetic mesh in abdominal wall hernias repair].
AB - Abdominal hernias repair beside cholecystectomy and appendectomy is the most
commonly performed surgical procedure. The crucial problem in surgery treatment
of abdominal hernias is its recurrence, especially high in procedures performed
without use of synthetic graft. Advances in understanding the etiopathogenesis of
abdominal hernias and the introduction of the new surgical techniques have
considerably improved the results of its repair. The widely used synthetic mesh
is made of durable material and its structure enables easy and safety
intraperitoneal implantation also in laparoscopic surgery. Unfortunately the high
cost of this procedure limits its use. There is still need for 'ideal' mesh
material and high hope for increasing biological graft application in the future.
PMID- 22046823
TI - [Use of polymeric clips in laparoscopic appendectomy].
AB - The aim of this study was to evaluate efficiency and safety of using non
absorbable polymeric clips in securing the stump of appendix during laparoscopic
appendectomy. PATIENTS AND METHODS: We have analyzed patients of Surgical Clinic
of 4th Military Clinical Hospital in Wroclaw, who underwent laparoscopic
appendectomy from 2006 to 2010. Patients were divided into 3 groups regarding to
the way of securing stump of appendix: in group one non-absorbable polymeric
clips Hem-o-lok were used, in group two endostaplers Endostapler Flexi and in
group three endoloop ligatures or traditional ligatures. Evaluated data included
operative time, intra- and postoperative complications, hospital stay and costs
of used materials. RESULTS: There were performed 90 laparoscopic appendectomies
between 2006 and 2010 in Surgical Clinic of 4th Military Clinical Hospital in
Wroclaw. Non-absorbable polymeric clips Hem-o-lok were used in 30 patients,
endostaplers in 27 and endoloop ligatures in 33 cases. There were no intra- and
perioperative complications such as bowel injury, appendix stump leak or early
bowel obstruction. Two cases of postoperative pericaecal (perityphlic) abscess (1
in group one, 1 on group two) were observed, in both cases antibiotic therapy was
successive, patients didn't require surgery. Wound infection was observed in 3
cases (2 in group one, 1 in group three). Mean operative time was 70,5 min. in
group one (from 40 to 115 min.), in group two 58,5 min. (from 25 to 110 min.),
and in group three 76,3 min. (from 40 to 120 min.). Mean hospital stay was 2,6
days in group one (from 2 to 4 days), in group two 2,9 days (from 2 to 7 days.),
and in group three 2,88 days (from 2 to 8 days). CONCLUSIONS: Using of non
absorbable polymeric clips Hem-o-lok is an efficient and safe way of securing the
stump of appendix during laparoscopic appendectomy, comparing to other methods
(endostapler and Endoloop ligature). Advantages of polymeric clips are facility
of application (most of surgeons have experience in clips application during
performed for many years laparoscopic cholecystectomies) and low cost (comparing
to endostaplers).
PMID- 22046824
TI - [Analysis of antibiotic diffusion from agarose gel by spectrophotometry and laser
interferometry methods].
AB - The aim of this study was to analysis of antibiotics (ampicilin, streptomycin,
ciprofloxacin or colistin) release from agarose gel by spectrophotmetry and laser
interferometry methods. The interferometric system consisted of a Mach-Zehnder
interferometer with a He-Ne laser, TV-CCD camera, computerised data acquisition
system and a gel system. The gel system under study consists of two cuvettes. We
filled the lower cuvette with an aqueous 1% agarose solution with the antibiotics
at initial concentration of antibiotics in the range of 0.12-2 mg/ml for
spectrophotmetry analysis or 0.05-0.5 mg/ml for laser interferometry methods,
while in the upper cuvette there was pure water. The diffusion was analysed from
120 to 2400 s with a time interval of deltat = 120 s by both methods. We observed
that 0.25-1 mg/ml and 0,05 mg/ml are minimal initial concentrations detected by
spectrophotometric and laser interferometry methods, respectively. Additionally,
we observed differences in kinetic of antibiotic diffusion from gel measured by
both methods. In conclusion, the laser interferometric method is a useful tool
for studies of antibiotic release from agarose gel, especially for substances are
not fully soluble in water, for example: colistin.
PMID- 22046825
TI - [The effect of the composition of stomatological dressings on Carbopol 971P and
methylocelullose base on pharmaceutical availability of metronidazole].
AB - The carried out studies allowed to propose composition of stomatological dressing
makes opportunity to ensure preferable physiochemicals features for dosage forms.
According to results formulations contain 1.5% Carbopol 971P, 0.13%
methylocelullose and various quantity of glycerol, 1,2-propylene glycol and
polyethylene glycol 400 were prepared. To compare formulation consists of only
polymers dispersion (Carbopol 971P and methylocelullose) was prepared. Next to
produced compound triethanoloamine to pH range 5.5-6.5 and 1% metronidazole
added. Kinetics test of metronidazole release was performed in vitro using
Hanson's cells and semipermable membrane. The quantity of the release
metronidazole was determined by spectrophotometric method. Gel consists of 98%
polymers dyspersion with 2% glycerol characterized by the largest pharmaceutical
availability. The addition of 2% PEG 400 resulted in the decrease of the
percentage of released substance in comparison to formulation without
hydrophylisers. Metronidazole releasing was more efficient for dressings with 2%
glycerol as well propylene glycol. For preparations contains glycerol (2 and 5%)
as well propylene glycol as adiuvants, it was found that gels prepared on
Carbopol 971P and methylocelullose revealed higher pharmaceutical availability
than analogical dressings prepared with only one polymer base.
PMID- 22046826
TI - Extraction characterization and evaluation of selected mucilage as pharmaceutical
excipient.
AB - Natural polymers have been used in different pharmaceutical formulations. They
are easily available, non-toxic, biodegradable and cost effective to be used as
pharmaceutical excipient. In present investigation mucilage was extracted from
fruit of Hibiscus esculentus and further characterized to be used as
pharmaceutical excipient. Tablets were prepared using four different
concentrations (6.6%, 13.3%, 20%, 26.66%) of Hibiscus esculentus mucilage and
potato starch to evaluate binding properties of mucilage. Results obtained from
the micromeritic characterization and flow behavior showed that Hibiscus
esculentus mucilage is a good candidate to be used as pharmaceutical excipient.
Tablets prepared using mucilage showed relatively lesser friability than prepared
with starch. It was found that release of drug from tablets prepared with
mucilage was less as compared to prepared with starch. Findings of the different
results easily predict the fact that mucilage obtained from Hibiscus esculentus
has characteristics to be used as pharmaceutical excipient.
PMID- 22046827
TI - Preparation, characterization and application of chitosan-alginate based
polyelectrolyte complex as fast disintegrating drug delivery carrier.
AB - AIM: Present investigation was carried out with aim to synthesize chitosan
alginate polyelectrolyte complex, their characterization and then formulation of
phenytoin sodium fast dispersible tablet using polyelectrolyte as active
excipient. METHODS: In this study, polyelectrolyte complex was formed by ionic
cross-linking of polymers. Dried complex was evaluated for micromeritic
properties and flow behaviour. Tablets were prepared for six batches based on
different proportion of complex viz 5%, 10%, 20%, 30%, 40%, 50% and 60%. Tablets
were evaluated for hardness, friability, thickness, in vitro disintegration time,
in vitro dissolution study and stability study. RESULTS: Results of micromeritic
study and flow behaviour predict that complex can be used as an efficient
excipient. Hardness, friability, thickness all were in acceptable limit. Release
studies were showed that tablets release drug up to 99.97%. Batch showed .sec of
invitro disintegration time. Stability study easily predicted that formulation
characteristics dose not changed during the whole period of study. CONCLUSIONS:
From the findings it is concluded that chitosan-alginate polyelectrolyte complex
is efficient excipient for fast dispersible formulation especially required in
case of epilepsy and chronic diseases.
PMID- 22046828
TI - [Density form of Kedem-Katchalsky equations for non-electrolyte solutions].
AB - A method of transformation of the Kedem-Katchalsky equations from concentration
to density form was presented. These equations were applied for mathematical
description of the volume flux (J(v)) through polymeric membrane in concentration
polarization conditions, i.e. in existence on both sides of the membrane of
concentration boundary layers (l(l), l(h)). Obtained model is the cubic equation,
in which coefficients contain the membrane transport parameters (L(p), sigma,
omega), density of solutions (rho(l), rho(h)), diffusion coefficients in layers
(D(l), D(h)) and thicknesses of l(l) and l(h). Assuming that the layers l(l) and
l(h) are symmetric (delta(l) = delta(h) = delta) and coefficients D(l) and D(h)
are not dependent on concentration, the suitable transformation of model for J(v)
the square equation for delta was obtained.
PMID- 22046829
TI - [Modification of the Katchalsky's relation between effective and real solute
permeability coefficients through polymeric membrane].
AB - Using Kedem-Katchalsky equations, in which volume (J(v)) and solute (J(s)) fluxes
are functions of the osmotic (delta(pi)) and hydrostatic (deltaP) driving forces,
the mathematical model for zeta(s) parameter was elaborated. This parameter
describes relation between effective and real solute permeability coefficients
through a membrane. Calculations performed on the basis of obtained quadratic
equation show that for a polymeric membrane with fixed transport properties
parameter zeta(s) is nonlinear function of solution concentration. This
nonlinearity is caused by a change of distance between a system and stable state
of diffusion. The reason of this nonlinearity is change of distance between a
system and stable diffusion state. The appearance of instability related with
breaking of symmetry of concentration boundary layers relative to the gravitation
direction causes increases of the coefficient value. This is the sign of
appearance of diffusion-convection of mass transport.
PMID- 22046830
TI - [Dyspnea, what is the cause? Rhabdomyosarcoma].
PMID- 22046831
TI - [Physician office preemption should help reduce oversupply. Practice purchase by
national health insurance is not necessarily a loss].
PMID- 22046832
TI - [Drugs, diabetes, nutrition, operations: in elderly patients much is different].
PMID- 22046833
TI - [When muscle strength declines in the elderly: prescribe sports and body building
food!].
PMID- 22046834
TI - [Therapy of Hodgkin lymphoma: chances of remission are good, treatment tolerance
needs improvement].
PMID- 22046835
TI - [Emergency in general practice].
PMID- 22046836
TI - [Emergency management in general practice].
PMID- 22046837
TI - [Experiences with functional neural therapy].
PMID- 22046838
TI - [Therapy of moderately severe depressions in daily practice: first patient care
research study reinforces clinical data].
PMID- 22046839
TI - [Rhinitis during pregnancy].
PMID- 22046840
TI - [Hypothyroidism as a rare cause for pericardial effusion in a growth-restricted
18-year-old].
PMID- 22046841
TI - [Atrial fibrillation--a complication in hypertension].
PMID- 22046842
TI - [Nocturnal enuresis].
PMID- 22046843
TI - Health care provider tobacco cessation counseling among current African American
tobacco users.
AB - Tobacco use is the leading cause of preventable mortality and morbidity in the
United States. Patients advised to quit use of tobacco products by their health
care providers are more likely to quit, yet it has been documented that patients
are not receiving this advice. The aim of this study was to investigate whether
or not current African American tobacco users were receiving provider-initiated
advice to quit. A cross-sectional survey identified 245 self-reported African
American tobacco users residing in Maryland. Study variables collected included
sociodemographics, access to care, smoking status, and assessed if tobacco
cessation counseling was ever provided. Among those surveyed, only 42% reported
ever being counseled to quit tobacco use and, of those who had a recent clinical
encounter (within the past year), only 20% reported being counseled. Multivariate
logistic regression identified that having a regular source of health care,
living in an urban setting, and being female increased chances of being advised
to quit tobacco use. Overall, findings indicate that African Americans are not
being screened or receiving cessation counseling as recommended by leading health
agencies. Health care provider training to promote better integration of tobacco
screening and tobacco cessation counseling during the patient encounter is
needed.
PMID- 22046844
TI - Perceptions of colorectal cancer among three ethnic subgroups of US blacks: a
qualitative study.
AB - Colorectal cancer (CRC) is currently associated with one of the highest burdens
of morbidity and mortality among American men and women. Racial/ethnic
disparities are well documented and the subject of intense research and
intervention. Our understanding of disparities related to awareness and
perceptions about causes, risk factors, and screening for CRC among subgroups of
blacks in the United States is limited. This may be in part because grouping US
born blacks and foreign-born blacks as one homogeneous group obscures possible
within-group differences. This study aimed to explore the cultural perceptions of
CRC among 3 ethnic subgroups of blacks: African Americans (US born), foreign-born
blacks from English-speaking Caribbean countries, and Haitian-born blacks. The
study was informed by a community-based participatory research approach, using a
cross-sectional mixed qualitative and quantitative methods design. A total of 62
individuals from the 3 ethnic subgroups participated in semistructured, in-depth
qualitative and structured quantitative interviews. Qualitative findings revealed
no stark differences among the 3 ethnic subgroups in their overall perceptions of
cancer as well as their attitudes related to barriers, motivation, and resources
for CRC screening. However, there were subtle differences in perceptions of
curability, preventive practices, and preferred sources of information among the
three ethnic subgroups of US blacks. The study has important implications for the
design of educational materials and targeted interventions for diverse groups of
US blacks.
PMID- 22046845
TI - Screening adherence for colorectal cancer among immigrant Hispanic women.
AB - PURPOSE: We sought to assess factors related to colorectal cancer (CRC) screening
adherence among immigrant, Hispanic women in Harlem, New York City. METHOD:
Adherence for colonoscopy and fecal occult blood test (FQBT) screening was
measured among 255 women based on self-reported screening behaviors using
American Cancer Society guidelines. RESULTS: Univariate results showed that age,
language of the interview (English/Spanish), years in the United States,
physician recommendation for either test, marital status (living alone/living
with someone), and mammography adherence were associated with CRC screening
adherence (p's < .05). In the multivariate analysis, having an age greater than
65 years, being interviewed in Spanish, having lived in the United States longer,
having a regular doctor and a physician recommendation, and being currently
adherent for mammography were associated with higher CRC screening adherence.
CONCLUSION: Among this sample, there proved to be differences between having ever
been screened and adherence with a greater proportion of women having ever
completed either colonoscopy and/or FOBT compared to women who were adherent
(72.9% vs 58.8%). Therefore, it is important to determine factors associated with
adherence, not just screening utilization, in order to design strategies to
increase adherence among immigrant Hispanic women.
PMID- 22046846
TI - Smoking and cancer: a review of public health and clinical implications.
AB - The cultivation of tobacco dates backwards to 6000 BC. Use of tobacco for
spiritual, euphoric, and medicinal purposes, and its ultimate spread to the 4
corners of the globe, lay at the heart of the current pandemic of tobacco-related
disease, including lung, head and neck, and many other forms of cancer. While
evidence for the carcinogenic properties of tobacco was documented as early as
the 1800s, it was not until the 20th century that the role of tobacco use and
smoke exposure in the growing pandemic of lung and other cancers was fully
appreciated. The evidence is now indisputable, and current research and
intervention activities center on mechanisms by which tobacco use and smoke cause
cancer, ways of stemming the worldwide pandemic of tobacco-related disease, and
how to help people with cancer quit smoking. With respect to the latter,
approaches to smoking cessation that are effective for the general population of
smokers are equally applicable to cancer patients, thrusting physicians and other
health professionals to the forefront of the antismoking arena. However, the
scale of the tobacco pandemic has grown so large that it literally will take a
village, complete with heads of nations, world-governing bodies, local leaders,
physicians, and many others, to pass and enforce legislation and policies
necessary to stem the worldwide tobacco pandemic and to implement cessation
programs for smokers and users of other forms of tobacco across the globe.
PMID- 22046847
TI - Patients' barriers to receipt of cancer care, and factors associated with needing
more assistance from a patient navigator.
AB - BACKGROUND: Racial minorities have poorer cancer survival in the United States
compared to whites. The purpose of this study was to better understand patients'
barriers to cancer care and to determine which patients have a greater need for
assistance from a patient navigator. METHODS: Community health workers assisted
newly-diagnosed breast and colorectal cancer patients during a randomized trial
of patient navigation and collected information about patients' barriers.
Barriers to care were characterized and compared between non-Hispanic white and
minority patients. A multivariate model was constructed of factors associated
with increased log navigation time, a measure of patients' need for assistance.
RESULTS: Patients' (n = 103) most commonly identified barriers to care included a
lack of social support, insurance/financial concerns, and problems communicating
with health care providers. Barriers differed between nonminority and minority
patients, and minority patients faced a greater number of barriers (p = .0001).
In univariate analysis, log navigation time was associated with race/ethnicity,
education, income, employment, insurance type, health literacy, marital status,
language, and comorbidity. A multivariate model (R2 = 0.43) for log navigation
time was created using stepwise selection, and included the following factors:
minority race/ethnicity (p = .032), non-full-time employment (p = .0004),
unmarried status (p = .085), university center (p = .0005), and months in study
(p <.0001). CONCLUSIONS: Newly diagnosed cancer patients' most common barriers to
care include lack of social support, insurance/financial concerns, and problems
with health care communications. In this sample of patients, a greater need for
assistance was independently associated with minority race/ethnicity and
unemployment. These data may help in the design and targeting of interventions to
reduce cancer health disparities.
PMID- 22046848
TI - Urban/rural patterns in receipt of treatment for non-small cell lung cancer among
black and white Medicare beneficiaries, 2000-2003.
AB - BACKGROUND: Receipt of treatment for lung cancer varies by a number of
demographic factors, including race/ethnicity and urban/rural residence. We
examined urban/rural patterns in receipt of treatment for non-mall cell lung
cancer (NSCLC) (ie, surgery, chemotherapy, radiation therapy) among black and
white Medicare beneficiaries in Alabama. METHODS: After linking Alabama State
Cancer Registry data with state Medicare data, we identified 3481 cases of stages
I to IV and unknown-stage NSCLC diagnosed from 2000-2002 and obtained their
treatment data for 1999-2003. We used bivariate and multivariate analyses to
examine racial and urban/rural differences in receipt of treatment. Significant
bivariate associations were tested using chi2 tests. RESULTS: Among beneficiaries
with resectable NSCLC (ie, stages I-IIIA), urban whites were more likely to
undergo surgical resection than urban blacks (49.3% vs 33.0%, respectively), and
more rural whites than rural blacks (49.8% vs 23.9%, respectively) underwent
surgery. There was less variation by race and urban/rural residence in the
receipt of chemotherapy and radiation therapy. After controlling for age at
diagnosis, gender, stage at diagnosis, comorbidity score, and socioeconomic
status, the racial disparity for surgery remained. Black beneficiaries in urban
counties had 45% lower odds of undergoing surgery than urban white beneficiaries
(OR, 0.55; 95% CI, 0.31-0.96), and those in rural counties had 67% lower odds of
receiving this treatment than their white counterparts (OR, 0.33; 95% CI, 0.19
0.57). CONCLUSIONS: Differences in receipt of surgery exist for both urban and
rural black Alabamians with NSCLC. Future studies should explore access to care
and perceptions about treatment among lung cancer patients in this state.
PMID- 22046849
TI - Cervical cancer screening among ethnically diverse black women: knowledge,
attitudes, beliefs, and practices.
AB - This is a descriptive study of cervical cancer screening knowledge, attitudes,
beliefs, and practices among ethnically diverse black women. We conducted 6 focus
groups with Haitian, African, English-speaking Caribbean, and African American
women recruited from a federally qualified health center. Overall, there was
limited knowledge and confusion across ethnic groups about cervical cancer and
its risk factors, the Pap test, and the human papilloma virus (HPV) and its
association with cervical cancer. At the same time, there were distinct
differences between ethnic groups in knowledge, practices, and cultural beliefs
about cervical cancer. African women knew the least among all the groups, while
African American participants had the greatest knowledge of HPV. However, their
knowledge was still limited. Patient-doctor relationship was the single most
important facilitator for cervical cancer screening. Barriers to cervical cancer
screening included cost, busy work schedule, fear of the unknown, lack of
insurance or being unemployed, and fear of disclosing immigration status.
Interventions with ethnically diverse black women would benefit from recognizing
cultural barriers and misconceptions that vary by ethnic group. Culturally based
strategies suggested by the focus groups include the use of existing social
networks, the use of indigenous community-based health workers, and the inclusion
of women of all ages in cervical cancer education because of the roles they have
in extended families.
PMID- 22046850
TI - Strategies used and challenges faced by a breast cancer patient navigator in an
urban underserved community.
AB - Patient navigation has been widely implemented by cancer care programs across the
United States. While activities of navigators have been described elsewhere,
little has been documented regarding specific strategies used or challenges
experienced by navigators from their own perspectives. We describe the experience
of an African American patient navigator who promoted breast cancer screening and
facilitated diagnosis and treatment among inner-city mostly African American
women in Newark, New Jersey. We conducted qualitative analysis of journal notes,
log data, and in-depth interviews with the patient navigator. Strategies used by
the patient navigator to develop trust and rapport included: (1) "meet patients
where they are" (outreach is best performed in locations women frequent, such as
hair salons); (2) being accessible (must be flexible and available by phone or in
person to meet patient's needs); and (3) "bring it down, sista" (must have
"street credibility" in dress and language). Key challenges included experiencing
threats to safety, setting boundaries, and facing and overcoming burnout. The
patient navigator responded to these obstacles by creating new community linkages
and resources and reaching out for emotional support from her mother and
supervisor. Areas that need to be addressed further for future patient navigator
programs include promoting safety in potentially dangerous neighborhoods and
helping navigators set boundaries and avoid burnout. Further research into
experiences of patient navigators in different settings is needed to build upon
this preliminary data, and to consider character traits and attributes best
suited for a patient navigator, as well as the support needed for this new health
care worker.
PMID- 22046851
TI - A cluster randomized controlled trial to increase breast cancer screening among
African American women: the black cosmetologists promoting health program.
AB - BACKGROUND: African American women have disproportionately higher rates of breast
cancer mortality than all other ethnic groups, thus highlighting the importance
of promoting early detection. METHODS: African American women (N = 984) from San
Diego, California, participated in a randomized controlled trial testing the
efficacy of breast cancer education sessions offered in beauty salons.
Cosmetologists received ongoing support, training, and additional culturally
aligned educational materials to help them engage their clients in dialogues
about the importance of breast cancer early detection. Posters and literature
about breast cancer early detection were displayed throughout the salons and
cosmetologists used synthetic breast models to show their clients how breast
cancer lumps might feel. Participants in the control group received a comparable
diabetes education program. Baseline and 6-month follow-up surveys were
administered to evaluate changes in women's breast cancer knowledge, attitudes,
and screening behaviors. RESULTS: This intervention was well received by the
participants and their cosmetologists and did not interfere with or prolong the
client's salon visit. Women in the intervention group reported significantly
higher rates of mammography compared to women in the control group. Training a
single educator proved sufficient to permeate the entire salon with the health
message, and salon clients agreed that cosmetologists could become effective
health educators. CONCLUSIONS: Cosmetologists are in an ideal position to
increase African American women's breast cancer knowledge and adherence to breast
cancer screening guidelines.
PMID- 22046852
TI - Barriers to colorectal cancer screening among publicly insured urban women: no
knowledge of tests and no clinician recommendation.
AB - OBJECTIVES: To assess barriers to colorectal cancer screening among urban
publicly insured women and to evaluate how barriers among underscreened urban
women have changed between 2001 and 2007-2008. METHODS: Eligible women were
selected using Medicaid Managed Care Organization (MMCO) administrative data.
MMCO outreach staff interviewed women by phone between October 2007 and February
2008, and assessed their barriers to colorectal cancer screening. We compared the
results of these interviews with interviews conducted in 2001 with women in
community health center waiting rooms. RESULTS: Thirty percent of overdue women
had never heard of either colonoscopy or sigmoidoscopy, and 55% had never heard
of home fecal occult blood testing (FOBT). Among overdue women who had heard of
colonoscopy or sigmoidoscopy, 33% reported misconceptions and 28% reported worry
as a barrier. No clinician recommendation was the most commonly reported barrier
to home FOBT (44%) and was also reported as a barrier to endoscopy by 22% of
women. Between 2001 and 2007-2008, the proportion of women reporting that they
had not received a clinician's recommendation for endoscopy or home FOBT
increased significantly. CONCLUSIONS: A lack of information, no clinician
recommendation, misconceptions, and worry persist as barriers to colon cancer
screening among this underscreened urban population. An increased focus on
clinician recommendation and patient education about stool-based as well as
endoscopic screening methods could lead to greater screening compliance.
PMID- 22046853
TI - Early hospital discharge following breast cancer surgery in the West Indies: a
Trinidad study.
AB - PURPOSE: To examine the outcome of a policy of early hospital discharge (<24
hours) after breast cancer surgery in a Third World setting, where health care
resources and support services are very limited. DESIGN: Prospective enrollment
into a plan of early hospital discharge within 24 hours following breast surgery.
Followup was conducted for wound infections; seroma formation; flap dehiscence;
and readmission, if any. SUBJECTS: All patients over a 15-year period who
underwent wide local excision or mastectomy and axillary clearance were enrolled.
RESULTS: A total of 331 patients were entered into the study. Of these, 148 had
modified radical mastectomy and 183 had wide local excision plus axillary
dissection. Each patient had a drain placed and output was recorded. Follow-up
revealed that there was no increase in the complication rates. CONCLUSION: Early
hospital discharge following breast cancer surgery is a feasible option for most
patients and can be safely implemented even in a resource-limited setting where
cost containment is essential.
PMID- 22046854
TI - T4b breast masses: a retrospective review of 12 cases presenting to a
metropolitan tertiary care center.
AB - INTRODUCTION: Due to increased awareness of breast cancer resulting in early
detection, there is a decreased incidence nationwide of late-stage breast cancer,
including that which presents with skin involvement (T4b). METHODS: A
retrospective analysis of a 10-month period from August 2007 to May 2008 at
Howard University Hospital (HUH), Washington, DC, revealed 12 patients diagnosed
with T4b breast cancer and compared to similarly staged patients in the
Surveillance, Epidemiology, and End Results (SEER) database. Finally, a logistic
regression for the likelihood of T4b diagnosis was performed patients in the SEER
database. RESULTS: HUH patients with T4b tumors were more likely than SEER
patients to present with predictors of poor clinical outcome, including high
grade histology (100% vs 59.4%, p = .04) and estrogen receptor- (75% vs 30.3%, p
= .001) and progesterone receptor- negative (91.7% vs 43.9%, p = .001) status.
Conversely, HUH patients were younger (57.8 y vs 66.3 y, p = .03) and had smaller
tumors (11.1 cm vs 28.2 cm, p = .02) than SEER patients with similarly staged
tumors. Older patients (OR, 2.36; 95% CI, 1.50-2.00; p < .001; 60-80 y), African
American patients (OR, 1.63; 95% CI, 1.26-2.11; p < .001), and patients with high
grade (OR, 5.51; 95% CI, 3.88-6.52; p < .001) tumors were more likely to be
diagnosed with T4b tumors, whereas patients who lived in an area with increased
median household income (OR, 0.99; 95% CI, 0.99-0.99; p = .001) were less likely
to be diagnosed with a T4b lesion. CONCLUSION: While much research has focused on
the socioeconomic causes for the development of T4b tumors, both patient and
tumor biologic conditions cannot be eliminated as causative agents.
PMID- 22046855
TI - A multimodal intervention to promote mammography and colorectal cancer screening
in a safety-net practice.
AB - BACKGROUND: There are limited data regarding interventions designed to improve
cancer screening rates in safety-net practices with "real world" patients.
OBJECTIVE: To examine the impact of a multimodal intervention on mammography and
colorectal cancer (CRC) screening rates in a safety-net practice caring for
underserved patients. METHODS: At an inner-city family medicine practice, all
patients past due for mammography or CRC screening were assigned to receive or
not receive a screening promotion intervention based on their medical record
number. The 12-month intervention included outreach to patients (tailored
letters, automated and personal phone calls) and point-of-care patient and
clinician prompts. The trial was registered at clinicaltrials.gov, NCT00818857.
RESULTS: We enrolled 469 participants aged 40 to 74 years, including 28% African
Americans, 5% Latinos, 25% with Medicaid, and 10% without any form of insurance.
Participants in the intervention group showed statistically significantly higher
rates of cancer screening; rates were 41% vs 16.8% for mammography and 28.8% vs
10% for CRC screening. These findings were confirmed in multivariable analysis.
Similar relative improvements in screening were seen across race, ethnicity,
socioeconomic status, and insurance groups. DISCUSSION: A multimodal intervention
shows promise for improving rates of mammography and colorectal cancer screening
within a safety-net practice. Further study will identify the most cost-effective
components of the intervention.
PMID- 22046856
TI - Cause for concern: the state of affairs of adjuvant breast radiation among
minority women with breast cancer.
PMID- 22046857
TI - Mortality with fracture of the femur in African Americans in 2005-2006.
PMID- 22046858
TI - The imperative for race-specific neutrophil count reference intervals in white
cell count evaluation.
PMID- 22046859
TI - [The European guidelines on residency training in anesthesiology, pain, and
intensive care].
PMID- 22046860
TI - [Residency training in anesthesiology].
PMID- 22046861
TI - [An established anesthesia team-care model: over 12000 cases in a digestive
endoscopy unit].
AB - BACKGROUND AND OBJECTIVE: The growing demand for digestive and other endoscopic
procedures outside the operating room, both in terms of type of endoscopy and
number of patients, requires reorganization of the anesthesiology department's
workload. We describe 2 years of our hospital digestive endoscopy unit's
experience with a now well-established care model involving both
anesthesiologists and nurse anesthetists. MATERIAL AND METHODS: After previously
reviewing the medical records of outpatients and conducting a telephone interview
about state of health, nurse anesthetists administered a combination of propofol
and remifentanil through a target-controlled infusion system under an
anesthesiologist's direct supervision. RESULTS: The ratio of anesthesiologists to
nurses ranged from 1:2 to 1:3 according to the complexity of the examination
procedure. Over 12000 endoscopies (simple to advanced) in a total of 11853
patients were performed under anesthesia during the study period. Airway
management maneuvers were required by 4.9% of the patients; 0.18% required bag
ventilation for respiratory depression, and 0.084% required bolus doses of a
vasopressor to treat hypotension or atropine to treat bradycardia. The procedure
had to be halted early in 9 patients (0.07%). No patient required orotracheal
intubation and none died. Nor were any complications related to sedation
recorded. CONCLUSION: The results suggest that this care model can safely
accommodate a large caseload in anesthesia at an optimum level of quality.
PMID- 22046862
TI - [Ephedrine vs. phenylephrine by intravenous bolus and continuous infusion to
prevent hypotension secondary to spinal anesthesia during cesarean section: a
randomized comparative trial].
AB - OBJECTIVE: Subarachnoid spinal anesthesia for cesarean section is associated with
a high incidence of hypotension, which can require the use of vasoconstrictors.
The aim of this trial was to compare ephedrine to phenylephrine for the
prevention of secondary hypotension and to assess the adverse effects on both
mother and newborn. MATERIAL AND METHODS: Eighty patients undergoing elective or
emergency cesarean section, in the absence of uterine activity or fetal risk,
were randomized to receive prophylaxis with ephedrine or phenylephrine
immediately after the spinal block. Patients in the ephedrine group received an
intravenous bolus of 0.1 mg/kg plus continuous infusion at a rate of 0.5 mg/kg/h;
patients in the phenylephrine group received an intravenous bolus of 1.5
microg/kg plus a continuous infusion at 1.5 microg/kg/min. Infusion was
maintained until umbilical cord clamping. We recorded maternal blood pressure,
heart rate, nausea and vomiting, dizziness, bradycardia, hypotension,
hypertension, fetal Apgar index, and umbilical cord blood parameters (pH, PCO2,
and HCO3). RESULTS: The overall incidence of hypotension was 11.2%, with no
significant between-group differences (ephedrine group, 11.4%; phenylephrine
group, 11.1%). The incidences of hypertension and bradycardia were higher in the
phenylephrine group (27.8% and 2.3%, respectively) than in the ephedrine group
(25% and 0%, respectively). Umbilical cord blood parameters and Apgar scores were
similar. After suspension of continuous infusion, an episode of hypotension was
detected in 22.5% of the patients (72.2% of these patients were in the
phenylephrine group and 27.8% were in the ephedrine group). CONCLUSIONS: At the
doses of ephedrine and phenylephrine administered in this trial, the ability of
these drugs to prevent hypotension during cesarean section proved to be similar.
Higher incidences of adverse events (hypertension and bradycardia) were observed
in the phenylephrine group. No differences were observed in neonatal effects.
PMID- 22046863
TI - [Estimating the angle of left lateral decubitus position during cesarean section:
observational study of anesthesiologists' estimates and of midwives and nurses'
level of understanding].
AB - OBJECTIVES: To determine the difference between the estimated and measured values
of the left lateral decubitus (LLD) angle in the positioning of patients for
scheduled cesarean section; to determine whether the accuracy of estimates
differs between staff anesthesiologists and residents; and to assess the angle
estimates of midwives and surgical nurses as well as their level of knowledge
with respect to the utility of the LLD position. METHODS: This was a prospective,
observational, double-blind study comparing staff anesthesiologists working in
obstetrics to residents in their second, third, or fourth-year of training. We
also presented a task and questions to midwives and surgical nurses who assisted
during categories 3 and 4 cesarean sections (elective and scheduled procedures)
according to the classification system of he National Institute of Clinical
Excellence. The anesthesiologist was asked to place the patient in LLD position
after onset of anesthesia and to estimate the LLD angle. A second
anesthesiologist measured the angle. The midwives and nurses were asked to place
a vacant surgical table at approximately 15 degrees; the angle was then measured.
Patient variables (weight, height, anesthetic technique) and staff variables
(position, understanding of the purpose of the maneuver, estimated DLL angle, and
measured angle) were recorded. RESULTS: Of 55 women who underwent cesarean
sections (98.18% under regional anesthesia), 25 were assessed by staff
anesthesiologists and 30 by residents. A total of 14 midwives and 10 surgical
nurses participated in the surgical table positioning task and answered
questions. The mean (SD) DLL angle estimate of the anesthesiologists was 12.4
degrees (3.4 degrees); the mean measured angle was 7.8 degrees (3.1 degrees). The
estimates of staff anesthesiologists were significantly more accurate (P < .001).
All the midwives understood the reason for using the DLL position in cesarean
section, while only 1 nurse (10%) did (P < .05). CONCLUSION: The DLL position
angle is overestimated by resident anesthesiologists and midwives. It seems that
the use and understanding of DLL positioning could be improved.
PMID- 22046864
TI - [Anesthetic conserving device (AnaConDa) used after cardiac surgery: experience
in a postoperative recovery unit].
AB - OBJECTIVE: To assess the safety and efficacy of using the Anesthetic Conserving
Device (AnaConDa) when maintaining sedation after cardiac surgery. MATERIAL AND
METHODS: Descriptive study of 46 consecutive patients in the postoperative
recovery unit after cardiac surgery between January and April 2009. The patients
were under sevoflurane sedation administered with the AnaConDa placed in the
inhalation tube. No exclusion criteria were established before enrollment. The
sevoflurane dose was set using the manufacturer's normogram and was later
adjusted to give an end-tidal concentration of sevoflurane between 0.5% and 0.7%
on the basis of data from a gas analyzer. Remifentanil was administered to all
patients; a fast-track extubation protocol was used. The only criterion for
excluding a patient's data from analysis was prolonged sedation (> 5 hours).
RESULTS: The mean (SD) time patients were under sedation with the AnaConDa in
place was 2588 (12.32) minutes. The end-tidal concentration of sevoflurane never
exceeded 1%. Scores on the Richmond agitation-sedation scale were -5 at 60
minutes in all cases; there was some score variability at 120 minutes. Deeper
sedation was desired for the first 60 minutes to avoid awakening related to
rewarming. The mean time until awakening was 6.17 minutes (range, 1-30 minutes).
The mean time until extubation was 43 (6.69) minutes. The most common adverse
effect was arterial hypotension (12 cases). Hypotension was related to bleeding
in 3 patients and to low cardiac output in 4 patients. CONCLUSION: Administering
sevoflurane through the AnaConDa can be a safe, valid, and reliable method for
sedating patients after cardiac surgery. With this device, it is possible to
monitor the concentration administered.
PMID- 22046865
TI - [Epiduroscopy].
AB - Epiduroscopy is a minimally invasive diagnostic and therapeutic technique used in
patients with chronic low back pain with or without radiculopathy. Epiduroscopic
procedures are particularly indicated in cases of failed spinal surgery. This
review discusses the indications, contraindications, and complications of the
technique, describing in detail the sacral (caudal) and interlaminar approaches
and noting their advantages and disadvantages. Practical recommendations are
made, along with an attempt to assess future prospects for epiduroscopy.
PMID- 22046866
TI - [Neurologic complications of central neuraxial blocks].
AB - Central neuraxial blocks, which are associated with a low incidence of
complications, are safe. When complications do occur, however, the resulting
morbidity and mortality is considerable. The reported incidence of complications
in all series is under 4 per 10000 patients, but given the absence of formal
registries and notification procedures, which have legal implications, the real
rate of occurrence of these rare events is uncertain. We searched the literature
through PubMed and the Cochrane Plus Library for a 5-year period, using the
search terms epidural anesthesia AND safety, spinal anesthesia AND safety,
complications AND epidural anesthesia, complications AND spinal anesthesia,
neurologic complications AND epidural anesthesia, and neurologic complications
AND spinal anesthesia. Neuraxial injury after a central blockade may be the
result of anatomical and/or physiological lesions affecting the spinal cord,
spinal nerves, nerve roots, or blood supply. The pathophysiology of neuraxial
injury may be related to mechanical, ischemic, or neurotoxic damage or any
combination. When a complication occurs, factors related to the technique will
have interacted with pre-existing patient-related conditions. Various scientific
societies have published guidelines for managing the complications of regional
anesthesia. Recently published clinical practice guidelines recommend ultrasound
imaging as a useful tool in performing a central neuraxial block.
PMID- 22046867
TI - [Reflections on residency training under the current recommendations of the
European Union of Medical specialists and the European Board of Anaesthesia
(UEMS/EBA guidelines)].
AB - The recent publication of guidelines for postgraduate training in anesthesiology,
pain, and intensive care issued by the European Board of Anaesthesia (EBA) and
the European Union of Medical Specialists (UEMS)
(http://www.sedar.es/revistasedar/uems.pdf) specifies directions we must take
with our residents. The training section of the Sociedad Espanola de
Anestesiologia y Reanimacion (SEDAR) has decided to make the guidelines available
on the association's website so that the UEMS/EBA proposals can be compared to
the training program drafted by the Spanish national board for our specialty. Our
aim is to identify points of convergence between the two proposals and to target
gaps where improvements can be made so that Spanish residency training in this
specialty is in harmony with the European framework.
PMID- 22046868
TI - [Inhalation anesthesia during spontaneous ventilation in a patient with a
tracheolaryngeal transplant requiring debridement of fibrous tissue obstructing
the lumen].
AB - Graft stenosis from fibrous granulation tissue is not an uncommon problem in
recipients of a transplanted trachea and larynx. We describe the case of a man
with a transplanted trachea who was seen for respiratory difficulty and stridor
secondary to stenosis. Examination through a rigid bronchoscope and surgical
debridement were both performed under anesthesia with sevoflurane alone while the
man breathed spontaneously. The outcome of treatment with sequential debridements
of fibrotic tissue and autologous stem cell injection was satisfactory and the
patient was discharged.
PMID- 22046869
TI - [Treatment of a female patient with sickle-cell anemia during cardiac surgery
with cardiopulmonary bypass].
AB - A 17-year-old girl with drepanocytic (sickle-cell) anemia who was being treated
with hydroxyurea and periodic blood transfusions through a Hickman-type catheter
was admitted for periodic episodes of fever. Blood cultures were positive for
methicillin-sensitive Staphylococcus aureus. Massive right atrial thrombosis with
pulmonary embolism and bacterial endocarditis were detected by computed
tomography. Surgery with a beating heart and cardiopulmonary bypass was
undertaken. Drepanocytic anemia in individuals homozygous for hemoglobin S is a
rare condition in Spain but we are beginning to see a few cases, in which
management during anesthesia will be more complicated. High-risk surgery can be
carried out in these patients without adverse events if the anesthesiologist is
guided by a complete blood workup and takes precautions during and after surgery
to control hydration, oxygenation, temperature, and the acid-base balance.
PMID- 22046870
TI - [Comments on the article "Hypotensive resuscitation of the polytrauma patient
with hemorrhagic shock"].
PMID- 22046871
TI - [Comments on the article "Perioperative anesthetic management of 300 morbidly
obese patients undergoing laparoscopic bariatric surgery and a brief review of
relevant pathophysiology"].
PMID- 22046872
TI - [Update on the use of opioids in acute, chronic, and breakthrough pain: an
international symposium. Barcelona, February 2011].
PMID- 22046873
TI - [Unusual placement of a central venous catheter].
PMID- 22046874
TI - [Vertebral-jugular fistula after central venous catheterization].
PMID- 22046875
TI - [Forgotten HEART day].
PMID- 22046876
TI - [Intimomedial thickness of the vertebral arteries complex: a new useful parameter
for the assessment of atheroclerotic process?].
AB - BACKGROUND/AIM: An integral part of Doppler ultrasound examination of cervical
blood vessels is determination of intimomedial thicknes (IMT) of the common
carotid. The aim of the study was to estimate the relations between IMT of the
common carotid and vertebral arteries in order to determine if the value of IMT
obtained on the vertebral artery could be applied in clinical practice. METHODS:
We measured IMT in a randomized, prospective and cross-sectional study, performed
on 50 persons both sexes (29 men and 21 women), at the age from 18 to 79 years
(mean age 52.4 +/- 17.63 years). All the persons were healthy, what was confirmed
with clinical examination and laboratory analyses. Measurements were perfomed
from January 2006 until September 2008. Intimomedial thickness was recorded by
two dimensional ultrasonography in B-mode on both common carotid arteries: one
value was obtained as average of three successeful measurements (measurements
were perform on different places). We measured IMT on the first segment of both
vertebral arteries, 1.5 cm proximal from the connection of the first and second
segments (we got results of the measurement of IMT on the vertebral arteries in
the same way: mean value from the three records). RESULTS: The measured value of
IMT on the common carotid arteries (IMT = 0.782 +/- 0.248 mm), obtained from 50
healthy persons, was higher than that measured on the vertabral artery on the
first segment (IMT = 0.585 +/- 0.134 mm). The values of IMT after measurement on
two different places were statistically highly different (t = 7.03, SD = 0.028, p
< 0.01). Coefficient of variability of IMT values in carotid circulation (CV =
34.4%) was higher than that in vertebral circulation (22.9%). Values of IMT on
vertebral arteries were in statistically significant correlation with those in
carotid circulation (r = 0.24 and t- = 2.48; p < 0.02). There were no
statistically significant difference between IMT measurement on the right and the
left side so they were analysed as the same set. CONCLUSION: Values of IMT on the
vertebral arteries are one more undependent parameter of Doppler-sonographic
examination of cervical vessels, which significantly correlates with IMT values
on common carotid artery. Variability of this parameter is lower, and absolute
values lower than the same in the common carotid artery. Therefore, this
parameter is probably not so sensitive. On the other hand, lower variability of
IMT values on the vertebral artery might be of higher specificity for prediction
of atherosclerotic progress by the increased values of this parameter than based
on IMT values obtained on the common carotid arteries.
PMID- 22046877
TI - Ultrasound measurement of visceral fat in patients with primary biliary
cirrhosis.
AB - BACKGROUND/AIM: Primary biliary cirrhosis (PBC) is a progressive, chronic liver
disease with elevated serum lipids, but it is unclear whether hyperlipidemia in
PBC patients is associated with atherosclerosis. Metabolic syndrome promotes
development of atherosclerotic cardiovascular disease related to abdominal type
obesity and insulin resistance. The aim of our study was to assess abdominal
adiposity in patients with PBC. METHODS: The study included 40 patients with PBC
and 50 healthy controls. Age, sex and anthropometric measurements (weight,
height, body mass index and waist circumference) were registered for all patients
and controls. We used ultrasonography to measure subcutaneous (SF) and visceral
fat (VF) diameter, subcutaneous area (SA) and visceral area (VA), as well as
perirenal fat diameter (PF). RESULTS: Values of SF, VF and PF thicknesses in PBC
patients were 19.23 +/- 5.85 mm, 10.92 +/- 3.63 mm, and 7.03 +/- 1.82 mm,
respectively. In controls these measurements were 22.73 +/- 6.70 mm, 16.84 +/
5.51 mm and 10.50 +/- 2.70 mm respectively. In PBC patients SA and VA were
calculated to 983.64 +/- 322.68 mm2 and 403.64 +/- 166.97 mm2 and in controls
1124.89 +/- 366.01 mm2 and 720.57 +/- 272.50 mm2 respectively. Significant
difference was found for VF, VA and RF values. CONCLUSIONS: Considering that the
amount of visceral fat plays an important role in development of metabolic
syndrome and cardiovascular diseases, we concluded that the lower amount of
visceral fat in PBC patients could be related to lower incidence of
cardiovascular events, despite hyperlipidemia.
PMID- 22046878
TI - [Endoscopic mucosal resection of colorectal tumors--our first experience].
AB - BACKGROUND/AIM: Endoscopic mucosal resection (EMR) or mucosectomy is an
interventional procedure for minimal invasive endoscopic removal of benign and
malignant digestive tract tumors. Mucosectomy removes flat and sessile neoplasms,
early colorectal cancer (CRC) confined to mucosa or submucosa and lateral
spreading tumors. The aim of the study was to show our first experience in
application of this procedure in everyday practice in regarding completeness and
efficacy of the procedure, complication rate and incidence of recurrent adenomas.
METHODS: In the prospective study 51 colorectal adenomas were removed in 44
patients by EMR. RESULTS: Single mucosectomy was done in 43 patients, while
multiple (8) in one patient. Complete resection was obtained in all procedures.
In 36 (68.62%) procedures "en block" resection was done, but in 15 (31.37%)
procedures "piece meal" resection was performed. Synchronous colorectal tumors
(benign or malignant) were detected in 20 (45.45%) patients. Moderate dysplasia
was found in 30 (58.82%) adenomas, but high grade dysplasia in 9 (17.64%) of
adenomas. Intramucosal CRC was detected in 11.77% of adenomas. A total of 37
(72.54%) advanced adenomas were removed. There were 3 (5.88%) of recurrent
adenomas, 6-30 months after the EMR. Only one (2.2%) case of post procedure
bleeding was observed. CONCLUSION: EMR is a safe and efficious method for removal
of flat, sessile adenomas, as well as early CRC. EMR is a routine endoscopic
procedure in everyday practice of interventional endoscopist.
PMID- 22046879
TI - [Influence of hemoglobin level and dose of administered recombinant human beta
erythropoietin on survival of hemodialysis patients].
AB - BACKGROUND/AIM: In patients with end-stage renal disease, treatment with
erythropoietin lowers cardiovascular morbidity, improves quality of life and
patient survival. The aim of this study was to determine the difference in
survival of hemodialysis patients treated with recombinant human beta
erythropoietin and patients without this treatment, and to determine the
influence of hemoglobin level and erythropoietin dose on the survival of these
patients. METHOD: The study included 291 patients undergoing maintenance
hemodialysis, 122 were on erythropoietin therapy, 169 patients formed control
group. The study was performed at the Clinic for Nephrology and Clinical
Immunology, Clinical Center of Vojvodina, during a 69-month period. We analyzed
basic demographic parameters, dialysis duration, underlying disease,
comorbidities, death causes, blood-work parameters and erythropoietin dosage.
Descriptive statistics, Anova, Manova, discriminant function analysis, Cox
regressional model and Kaplan Meier survival curves were used as statistical
methods. RESULTS: Average age and dialysis duration in the experimental group
were 47.88 +/- 13.32 years, and 45.76 +/- 46.73 months, respectively and in the
control group 58.73 +/- 12.67 years and 62.80 +/- 55.23 months, respectively.
Average level of hemoglobin and hematocrit in the group in which erythropoietin
had been administered was 11.40 +/- 8.39 g/dL and 0.35 +/- 0.04/L, while the
control group these values were 8.52 +/- 7.73 g/dL and 0.26 +/- 0.04/L,
respectively. Average monthly dosage of erythropoietin was 21 587 +/- 10 183.36
IJ/month. Significant difference in survival was determined (p < 0.05) between
the stated patient groups. A significant difference (p < 0.05) was found in
survival of the patients in which erythropoietin was administered regarding
hemoglobin level (< 100 g/L/100-110 g/L/110-120 g/L/ > 120 g/L), as well as in
regard of erythropoietin dose applied (< 20 000 IJ/20 000-40 000 IJ/ > 40 000
IJ/month). CONCLUSION: Best survival was noted in patients with hemoglobin > 120
g/L and erythropoietin dose < 20 000 IJ/month.
PMID- 22046880
TI - Influence of glucoregulation quality on C-reactive protein, interleukin-6 and
tumor necrosis factor-alpha level in patients with diabetes type 1.
AB - BACKGROUND/AIM: Results of studies which have proved an increased inflammatory
activity in diabetes type 1, have been published over recent years. One of
possible mechanisms that are used to explain chronic inflammation in diabetes is
the state of hyperglycemia leading to the enhanced synthesis of glycosylation end
products (AGEs) which activate macrophages, increase the oxidative stress and
affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha
(TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine
the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1
and to establish their correlation with glucoregulation parameters and other
cardiovascular risk factors as well as to compare them with the healthy controls.
METHODS: The study included 76 patients with diabetes type 1 and 30 healthy
controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and
glucoregulation parameters (fasting glucose HbA(1c)). RESULTS: The values of CRP
(p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically
significantly higher in the diabetic patients than in the healthy controls. There
was a positive correlation between CRP with postprandial glycemia (p = 0.004);
the multivariate regression analysis revealed a statistically significant
correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose
(p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL
cholesterol (p = 0.009). No statistically significant correlations were found
between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6
and TNF-alpha). CONCLUSION: The patients with type 1 diabetes were found to have
a low level of inflammatory activity manifested by the increased values of CRP,
IL-6 and TNF-alpha.
PMID- 22046881
TI - Bone bruise of the knee associated with the lesions of anterior cruciate ligament
and menisci on magnetic resonance imaging.
AB - BACKGROUND/AIM: Bone bruise is a common finding in acutely injured knee examined
by magnetic resonance (MR). The aim of the study was to determine the association
of bone bruise frequency with postinjury lesions of anterior cruciate ligament
(ACL) and menisci. Bone bruise involves posttraumatic bone marrow change with
hemorrhages, edema and microtrabecular fractures without disruption of adjacent
cortices or articular cartilage. MR imaging is a method of choice for detecting
bone bruises which can not be seen on conventional radiographic techniques.
METHODS: A representative review of 120 MR examinations for the acute knee trauma
was conducted. All the patients were examined within one month of trauma. All MR
examinations were performed by using a 0.3T MR unit. RESULTS: Posttraumatic bone
bruise was seen in 39 (32.5%) patients out of 120. Three patients had fracture of
the cortex, so-called "occult" fracture (not seen on plain radiography). We
analyzed only bone bruises without these fractures of the cortex. Bone bruise was
associated with the lesion of ACL in 27 (69%) patients. In 28 (72%) patients bone
bruise was in combination with the lesion of menisci. Only two patients with bone
bruise had neither ACL nor menisci lesions. There were 78 patients without bone
bruise but 33 (43%) of them had lesions of ACL and 49 (63%) had lesions of
menisci. CONCLUSION: Bone bruise is best seen in STIR (Short TI Inversion
Recovery) images and is very often found in acute knee trauma. Very often it is
associated with posttraumatic lesions of ACL and menisci, so attention must be
paid to this when bone bruise is seen. The difference in frequency of internal
structures of the knee lesions in patients with bone bruise is highly
statistically significant as compared to patients with no bone bruise.
PMID- 22046882
TI - Possibilities of nontoxic autonomous thyroid nodules treatment by percutaneous
ethanol injection.
AB - BACKGROUND/AIM: According to the current principles, autonomous functional
thyroid nodules are treated by surgery or by radioiodin therapy. Ultrasound
guided percutaneous ethanol injection into solid tumors of the soft tissues was a
starting point in attempts to treat the thyroid nodules by the same method. The
aim of the study was to assess the efficiency of percutaneous injection in
treating solitary, nontoxic, autonomous thyroid nodules of up to 15 mL volume.
METHODS: In 25 patients with solitary nontoxic autonomous thyroid nodules
diagnosed by tehnetium-99m scanning as an intensive area having a complete
supremacy in the paranodal tissue, an ultrasound guided percutaneous ethanol
injection was applied. The procedure was carried out repeatedly once a week until
the reduction in nodule size to 50% of the initial size was achieved. RESULTS: An
average size of the nodule before curing was 9.68 +/- 5.01 mL. An average
quantity of the injected ethanol was 9.52 +/- 5.08 mL, ie 1.06 +/- 0.48 mL/mg of
the tissue. The regression of the nodule size in the successfully (deltavol% u
57.09 +/- 13.75%, p < 0.001) and partly successfully cured (deltavol du = -48.45
+/- 14.35%, p < 0.05) was statistically significant compared to the size before
the treatment. After ceasing ethanol injection, 18 months later, a further size
regression (deltavol% = -79.20 +/- 9.89%) compared to the initial one (p < 0.001)
was noticed. Soon, after the procedure was finished, a statistically significant
concentration increase of Thyroid Stimulating Hormone (TSH) was noticed compared
to the initial values (0.18 +/- 0.16 vs 0.34 +/- 0.31 mU/L, p < 0.01). According
to the given criteria, in two female patients satisfactory results were not
achieved, but, a year later, in one of them the nodule was not seen by repeated
scintigram. The number and frequency of side effects were insignificant.
CONCLUSION: Repeated percutaneous ethanol injections into nontoxic solitary
autonomous thyroid nodules result in disappearing of authonomy. The regression of
the nodule size of more than 50% compared to its initial volume, as well as the
increase in concentration of TSH for more than 50% are the signs of a successful
treatment.
PMID- 22046883
TI - Arthroscopic partial medial meniscectomy.
AB - BACKGROUND/AIM: Meniscal injuries are common in professional or recreational
sports as well as in daily activities, If meniscal lesions lead to physical
impairment they usually require surgical treatment. Arthroscopic treatment of
meniscal injuries is one of the most often performed orthopedic operative
procedures. METHODS: The study analyzed the results of arthroscopic partial
medial meniscectomy in 213 patients in a 24-month period, from 2006, to 2008.
RESULTS: In our series of arthroscopically treated medial meniscus tears we noted
78 (36.62%) vertical complete bucket handle lesions, 19 (8.92%) vertical
incomplete lesions, 18 (8.45%) longitudinal tears, 35 (16.43%) oblique tears, 18
(8.45%) complex degenerative lesions, 17 (7.98%) radial lesions and 28 (13.14%)
horisontal lesions. Mean preoperative International Knee Documentation Committee
(IKDC) score was 49.81%, 1 month after the arthroscopic partial medial
meniscectomy the mean IKDC score was 84.08%, and 6 months after mean IKDC score
was 90.36%. Six months after the procedure 197 (92.49%) of patients had good or
excellent subjective postoperative clinical outcomes, while 14 (6.57%) patients
subjectively did not notice a significant improvement after the intervention, and
2 (0.93%) patients had no subjective improvement after the partial medial
meniscectomy at all. CONCLUSION: Arthroscopic partial medial meniscetomy is
minimally invasive diagnostic and therapeutic procedure and in well selected
cases is a method of choice for treatment of medial meniscus injuries when repair
techniques are not a viable option. It has small rate of complications, low
morbidity and fast rehabilitation.
PMID- 22046884
TI - Arterial hypertension in the elderly.
PMID- 22046885
TI - [Nutrigenomics--the science of the 21st century].
PMID- 22046886
TI - Successful implantation of a permanent pacemaker through a persistent left
superior vena cava by using a right subclavian approach.
AB - INTRODUCTION: Persistent left superior vena cava, a rare congenital abnormality,
can complicate placement of pacemaker leads through the subclavian vein. A left
sided approach is usually preferable in such cases. CASE REPORT: We reported a
case in which we began a single-chamber pacemaker implantation procedure via a
right subclavian approach (because of scarring beneath the left clavicle) and
then discovered intraoperatively that the patient had a persistent left superior
vena cava. After a few attempts, we succeeded in placing the head of the
electrode in the septum, near the top of the right ventricle, and the rest of the
procedure was completed without complication. CONCLUSION: To our knowledge, this
is the first reported case of pacemaker implantation, with passive electrode,
through a persistent left superior vena cava via the right subclavian vein. This
case demonstrates that such an approach, when necessary, can be used
successfully.
PMID- 22046887
TI - [Surgical treatment of unicentric plasma cell histological type Castleman's
disease].
AB - INTRODUCTION: Castleman's disease or angiofollicular lymph hyperplasia is a rare
disease with two identified clinical forms. Unicentric or localized form is
characterized by isolated growth of lymph nodes, most often in mediastinum, and
multicentric form is expressed as systemic disease with spread lymphadenopathy,
organomegaly and presence of general symptoms of the disease. Histological types
are hyalovascular, plasma-cell and transitive (mixed) cell. CASE REPORT: This
case report shows a woman, 59 years old, with unicentric form of plasma-cell type
of Castleman's disease. Unicentric form is usually shown as hyalovascular
histological type, extremely rare as plasma-cell type, and transitive (mixed)
cell type was never described in literature as localized clinical form. The
disease was manifested with chest pain, loss of body weight, exhaustion and
weakness of legs. Further diagnostic procedures found the presence of enlarged
lymph nodes paratracheally right, in a close contact with vena cava superior. The
disease was confirmed by histopathological analysis of bioptated mediastinal
lymph node after mediastinoscopy. Surgical treatment included extirpation of
enlarged lymph nodes. After the regular postoperative condition, a full therapy
effect was confirmed. CONCLUSION: Unicentric form of Castleman's disease is
expressed with enlarged lymph nodes on predilected places, usually in
mediastinum. Surgical treatment is best method for the management of the disease
and brings a full recovery of patient.
PMID- 22046888
TI - [Simultaneous phacoemulsification, lens implantation and endothelial keratoplasty
(triple procedure)].
AB - INTRODUCTION: Simultaneous Descemet stripping endothelial keratoplasty,
phacoemulsification, and intraocular lens implantation are indicated in Fuchs'
dystrophy with associated cataract. Compared to the standard method of the triple
procedure which includes penetrating keratoplasty, this new method has the
advantages of sutureless surgery, small limbal incision, faster recovery, less
surface problems, less astigmatism, stronger tensile strength and more
predictable calculation of the intraocular lens power. This is the first report
of such a combination of procedures in our literature. CASE REPORT: A 76-year-old
woman suffered from a gradual bilateral visual loss. The best corrected visual
acuity was 20/60 (right eye) and finger counting at 1m (left eye). Corneal
thickness was 590 microm and 603 microm, respectively. A marked cornea guttata
and nuclear cataract were present in both eyes. Phacoemulsification, lens
implantation, and Descemet stripping were done in the left eye. The posterior
lamellar corneal graft, 8.0 mm in diameter and about 150 microm thick, was bent
and inserted through the limbal incision. The air was injected into the anterior
chamber to attach the graft to the recipient stroma. The cornea remained clear,
and the transplant was attached during a two-year follow-up. Visual acuity was
20/40 after two months, and 20/25 after one year. CONCLUSION. The new technique
proved itself as a good choice for the treatment of a mild Fuchs' dystrophy
associated with cataract.
PMID- 22046889
TI - [Sacral gigantocellular tumor treated with total sacrectomy and spinal-pelvic
fixation].
AB - BACKGROUND: Total sacrectomy with spinal-pelvic fixation is considered to be a
successful approach to the radical surgical treatment of extensive sacral tumors,
however, technically very demanding, thus only rarely reported in the literature.
We presented a patient with sacral gigantocellular tumor managed successfully
using this method but with certain standard operative techniques improvements.
CASE REPORT: A 30-year old patient with a pronounced painful syndrome and
sphincter disorders was confirmed to have sacral gigantocellular tumor affecting
a greater part of the sacrum. Tumor resection was performed in the first act out
off retroperitoneal organs (colon and blood vessels), sacroiliac joints were open
by the ventral side, the L5 discus removed, the S2-S5 roots cut off. In the
second act, performed three weeks later, sacrectomy was completed by the
reconstruction of pelvic ring and spinal-pelvic fixation. Then, the standard
technique was modified to provide additional spinal fixation. The results of the
operation (duration, blood loss, postoperative deficit) were quite comparable
with, and in some aspects even better than the results published in the
literature. CONCLUSION: Total sacrectomy with spinal-pelvic fixation can be a
therapy of choice in patients with extensive sacral tumors requaring, however,
the multidisciplinary approach and a considerable experience with instrumental
spinal stabilization.
PMID- 22046890
TI - [Brain tumors in patients primarly treated psychiatrically].
AB - INTRODUCTION: Psychiatric symptoms are not rare manifestations of brain tumors.
Brain tumors presented by symptoms of raised intracranial pressure, focal
neurological signs, or convulsions are usually first seen by the neurologist or
less frequently by the neurosurgeon in routine diagnostic procedures. On the
other hand, when psychiatric symptoms are the first manifestation in
"neurologically silent" brain tumors, the patients are sent to the psychiatrist
for the treatment of psychiatric symptoms and brain tumors are left misdiagnosed
for a long period of time. CASE REPORT: We presented three patients with the
diagnosed brain tumor where psychiatrist had been the first specialist to be
consulted. In all three cases neurological examination was generally unremarkable
with no focal signs or features of raised intracranial pressure. CT scan
demonstrated right insular tumor in a female patient with obsessive-compulsive
disorder (OCD); right parietal temporal tumor in a patient with delusions and
depression and left frontal tumor in a patient with history of alcohol
dependency. CONCLUSION: Psychiatric symptoms/disorders in patients with brain
tumors are not specific enough and can have the same clinical presentation as the
genuine psychiatric disorder. Therefore, we emphasize the consideration of
neuroimaging in patients with abrupt beginning of psychiatric symptoms, in those
with a change in mental status, or when headaches suddenly appear or in cases of
treatment resistant psychiatric disorders regardless the lack of neurological
symptoms.
PMID- 22046891
TI - Time warp. Seeing people from the past.
PMID- 22046892
TI - Knowing. It's a key component of a successful career.
PMID- 22046893
TI - Just say no. With a drug test pending, an injured EMT wants no part of pain meds.
PMID- 22046894
TI - The executive EMS officer. What values and competencies does an EMS executive
need to succeed?
PMID- 22046895
TI - Orthopedic assessment. Injured extremities need not just be left for the
radiologist.
PMID- 22046896
TI - Virtual care. How telemedicine is transforming the delivery of emergency medical
services in the field.
PMID- 22046897
TI - 6 easy steps to weathering the financial storm. By dismissing the "victim"
mentality, you can create a blueprint to thrive.
PMID- 22046898
TI - Strategizing for success. When it comes to managing a volunteer agency, evaluate
operations much like you would patients to determine the best treatment option.
PMID- 22046899
TI - When hypoglycemia attacks. The devastating effects of long-term diabetes and
recurrent hypoglycemic events.
PMID- 22046900
TI - Transition series: topics for the EMT. Part 5: Soft tissue injuries: crush injury
and compartment syndrome.
PMID- 22046901
TI - Safer new world. It's on everyone's minds in the ambulance business, and about to
be move so.
PMID- 22046902
TI - Anal medics: don't be a-freud. The traits that annoy others may make you a better
caregiver.
PMID- 22046903
TI - Blended learning: an ideal combination for dental practice.
PMID- 22046904
TI - Contemporary adhesive bonding: bridging the gap between research and clinical
practice.
AB - The dawn of minimally invasive dentistry has led to the development of materials
which rely on the use of effective adhesion to bond to remaining tooth tissue.
Successful adhesive bonding is dependent upon appreciating the quality of the
dental substrate, appropriate clinical handling of the material and patient,
together with an appreciation of the chemistry of the adhesive. This paper
outlines the current status of contemporary bonding, with particular emphasis on
translating laboratory-based evidence into clinical practice. Using laboratory
based evidence, the ability of a bond to achieve a seal to enamel appears to be
the best predictor of clinical performance. CLINICAL RELEVANCE: This article
discusses the issues raised when translating research data about adhesive bonding
from the laboratory to clinical dental practice.
PMID- 22046905
TI - Aesthetic smile evaluation--a non-invasive solution.
AB - Enhancement of the aesthetic zone is a common reason for patients to seek dental
care. This article describes a protocol for the examination, assessment and
treatment planning for a patient seeking a solution to an aesthetic concern. The
technique of undertaking an intra-oral'mock-up' using resin composite as a
diagnostic approach can be particularly helpful when planning for future
prosthodontic rehabilitation. The latter can allow the operator and patient to
visualize crudely what is aesthetically and functionally possible, given the
constraints imposed by that patient. The patient has ultimately managed in a
minimally invasive manner. CLINICAL RELEVANCE: It can be very tempting for a
dental operator to impose his/her concepts of the'artistic ideal' when planning
for care in the smile zone. Such ideals are largely based on established
universal aesthetic principles of tooth colour, size, shape, form, position,
symmetry and proportion. However, beauty is a very subjective matter. It is
essential for the operator to listen attentively to his/her patient's concerns.
Meticulous patient examination and assessment are absolutely critical factors in
attempting to attain a successful outcome. The use of reversible, chairside intra
oral mock-up techniques can not only help with the transference of essential
information to the dental technician when planning for restorative intervention
in the smile zone, but can also allow the patient to gain an insight and indeed
contribute his/her views to the possible restorative endpoint, respectively.
PMID- 22046906
TI - Prosthodontic care for elderly patients.
AB - For older patients, clinicians should consider maintaining teeth and using
functionally-orientated treatment strategies as an alternative to removable
prostheses. When the remaining dentition has a poor prognosis, key teeth should
be preserved as overdenture abutments and a gradual transition to edentulousness
planned. Where complete dentures are provided, these can be retained using dental
implants to overcome many of the problems associated with conventional
replacement dentures. CLINICAL RELEVANCE: The elderly population of today is
better informed and more demanding of oral healthcare providers than previous
generations. Clinicians should be aware of all the prosthodontic treatment
options available for older patients.
PMID- 22046907
TI - Primary cutaneous CD8-positive T-cell lymphoma: a case report of a rare and
aggressive disease with oral presentation.
AB - A case of a 66-year-old man, who was referred to the Oral Medicine service with
persistent oral ulceration and widespread cutaneous rash is presented. Laboratory
investigations confirmed a diagnosis of epitheliotropic, CD8-positive, cytotoxic,
T-cell lymphoma. CLINICAL RELEVANCE: Oral ulceration represents a heterogeneous
group of aetiologies: the patient with this more concerning pathology presented
both to his general medical and dental practitioners.
PMID- 22046908
TI - 'Simultaneous technique' and a hybrid Microseal/PacMac obturation.
AB - In these endodontic case reports we present a root canal preparation protocol
using the Mtwo Ni-Ti rotary files according to the 'simultaneous technique' which
is a'crown-down' approach, where every instrument in the sequence is used to the
full working length. A hybrid Microseal/PacMac obturation (consisting of three
stages: master cone compaction, backfill with pre-plasticized guttapercha and
vertical compaction) is proposed in order to: maintain the obturation length
control associated with the Microseal system; use preheated gutta-percha to
backfill the canal rapidly with the PacMac condensor; and to reduce potential
voids in the obturation material with the final vertical compaction. CLINICAL
RELEVANCE: The'simultaneous technique'followed by apical preparation using Mtwo
apical files allows obturation using the proposed hybrid Microseal/Pacmac method,
aiming to overcome some of the shortcomings of the Microseal and Pacmac
obturation methods, such as length control difficulty and sealer pooling.
PMID- 22046909
TI - Sickle cell disease, dentistry and conscious sedation.
AB - The features of sickle cell disease (SCD) are described. Two case reports of
patients treated in a Dental Institute are presented and the dental management of
patients with SCD discussed. Since infection is one of the major risk factors for
sickle cell crisis, the prevention of oral disease and infection is vital for
this group of patients and there is no contra-indication to the delivery of
dental treatment under local anaesthetic with inhalational sedation if required
in the primary care setting. Since patients with sickle cell disease are
particularly vulnerable to the effects of periods of hypoxia, which may produce
significant morbidity, and because of the additional practical challenges in
sedating this group of patients, intravenous sedation should be undertaken in a
specialist unit. CLINICAL RELEVANCE: The increasing prevalence of sickle cell
disease highlights the importance of dentists practising in multi-cultural
communities having an understanding of this condition and its implications on
their clinical practice. This will facilitate the safe management of patients
with sickle cell disease.
PMID- 22046910
TI - 'Shenanigans at the General Dental Council'.
PMID- 22046911
TI - MHRA and CSD: here to help.
PMID- 22046912
TI - Fluoride in the media: a review of newspaper articles from 1999 to 2009 (Dent
Update 2011; 38:86-92).
PMID- 22046913
TI - Oral cancer: comprehending the condition, causes, controversies, control and
consequences. 9. Quality of life.
PMID- 22046914
TI - Technique tips--a novel isolation technique for multiple severely broken down
teeth requiring endodontic treatment.
PMID- 22046915
TI - Physical signs for the general dental practitioner. Case 87. Adrenal
insufficiency.
PMID- 22046916
TI - Safe staffing levers should be mandatory.
PMID- 22046917
TI - NMC and Unison clash over nurses' right to take industrial action.
PMID- 22046918
TI - RCN lobbies House of Lords in bid to secure mandatory staff ratios.
PMID- 22046919
TI - Head of Bahrain's nurses calls for backing of profession worldwide.
PMID- 22046921
TI - Health visitors still under pressure despite their recent 'renaissance'.
PMID- 22046920
TI - Lansley pledges to cut bureaucracy and drive up nursing care standards.
PMID- 22046922
TI - Redundancy is personal.
PMID- 22046923
TI - Packed and ready to go.
AB - Timely discharge from hospital is a fundamental part of care that requires staff
to be well trained, clear about their roles and open to innovative ideas.
PMID- 22046924
TI - Burning issue.
AB - Severe, persistent heartburn is a risk factor for a form of oesophageal cancer.
Increasing awareness of this link among health professionals and the public could
lead to earlier diagnosis and treatment.
PMID- 22046925
TI - Improving health outcomes for people with learning disabilities.
AB - Modern healthcare policy is driven by an emphasis on the philosophy of inclusion,
yet in the past decade there has been increasing recognition that people with
learning disabilities experience a range of difficulties when trying to access
general healthcare services. The Disability Discrimination Acts of 1995 and 2005,
and the Equality Act 2010, have driven service providers to find areas where
'reasonable adjustments' can be made to ensure improved health outcomes. This
article considers the background context as well as exploring what reasonable
adjustments mean in practice.
PMID- 22046926
TI - Pain assessment tools for older people with cognitive impairment.
AB - This article summarises and critiques various tools available for the assessment
of pain in older people with cognitive impairment. Definitions of pain are
numerous and are not always relevant to people with cognitive impairment because
these individuals are often unable to describe or communicate their pain. This
makes it difficult for healthcare professionals to assess the absence or presence
of pain in these patients. The aim of this article is to establish which of the
available pain assessment tools are most appropriate for use in older people with
cognitive impairment. From a review of the literature, the authors conclude that
pain assessment in older people with any degree of cognitive impairment is
complex and there is no gold standard.
PMID- 22046927
TI - Atrial fibrillation and primary stroke prevention.
AB - Atrial fibrillation (AF) is a common cardiac arrhythmia that significantly
increases the risk of ischaemic (embolic) stroke. The primary aim of this article
is to help healthcare practitioners understand the link between AF and stroke and
to assist them in assessing and managing high-risk patients. The association
between a cardiac arrhythmia and a disabling cerebral event is not always
understood fully. However, all healthcare professionals are in a position to
identify patients with AF.
PMID- 22046928
TI - Cancer cachexia.
PMID- 22046929
TI - Divine community care.
PMID- 22046930
TI - Meet with approval.
PMID- 22046931
TI - Dummy run.
PMID- 22046932
TI - Fluoride is an essential element of childhood oral health.
PMID- 22046933
TI - Histologic, microbial testing to confirm dermatologic conditions.
PMID- 22046935
TI - Improving adult immunization rates: overcoming barriers.
PMID- 22046936
TI - Better integration of mental health care improves depression screening and
treatment in primary care.
PMID- 22046937
TI - Opioid antagonists for the treatment of alcohol dependence.
PMID- 22046938
TI - Cognitive interventions for improving cognitive function.
PMID- 22046939
TI - Shave and punch biopsy for skin lesions.
AB - Shave and punch biopsies are essential procedures for physicians who manage skin
conditions. These office-based procedures can diagnose questionable dermatologic
lesions, including possible malignancies. Approaches include the superficial
shave biopsy, saucerization excision, punch biopsy, and elliptical excision. A
superficial shave biopsy can be used for raised lesions. A saucerization biopsy
may be performed for flat or pigmented lesions. Punch biopsies yield full
thickness samples and can be used for lesions that require dermal or subcutaneous
tissue for diagnosis. Indications for biopsy of suspected melanoma remain
controversial. Sufficient tissue may be obtained with the quicker, less costly
saucerization biopsy or the more time-consuming, invasive elliptical excisional
biopsy.
PMID- 22046940
TI - Causes and evaluation of mildly elevated liver transaminase levels.
AB - Mild elevations in levels of the liver enzymes alanine transaminase and aspartate
transaminase are commonly discovered in asymptomatic patients in primary care.
Evidence to guide the diagnostic workup is limited. If the history and physical
examination do not suggest a cause, a stepwise evaluation should be initiated
based on the prevalence of diseases that cause mild elevations in transaminase
levels. The most common cause is nonalcoholic fatty liver disease, which can
affect up to 30 percent of the population. Other common causes include alcoholic
liver disease, medication-associated liver injury, viral hepatitis (hepatitis B
and C), and hemochromatosis. Less common causes include alpha(1)-antitrypsin
deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic conditions
(e.g., thyroid disorders, celiac disease, hemolysis, muscle disorders) can also
cause elevated liver transaminase levels. Initial testing should include a
fasting lipid profile; measurement of glucose, serum iron, and ferritin; total
iron-binding capacity; and hepatitis B surface antigen and hepatitis C virus
antibody testing. If test results are normal, a trial of lifestyle modification
with observation or further testing for less common causes is appropriate.
Additional testing may include ultrasonography; measurement of alpha(1)
antitrypsin and ceruloplasmin; serum protein electrophoresis; and antinuclear
antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1
testing. Referral for further evaluation and possible liver biopsy is recommended
if transaminase levels remain elevated for six months or more.
PMID- 22046941
TI - Elevated liver enzymes.
PMID- 22046942
TI - Update on immunizations in adults.
AB - Vaccine-preventable diseases contribute significantly to the morbidity and
mortality of U.S. adults. The Advisory Committee on Immunization Practices of the
Centers for Disease Control and Prevention updates its recommended adult
immunization schedule annually. The most recent updates include the permissive
but not routine use of the quadrivalent human papillomavirus vaccine to prevent
genital warts in males; a single dose of herpes zoster vaccine for adults 60
years and older, regardless of their history; replacing a single dose of tetanus
and diphtheria toxoids (Td) vaccine with tetanus, diphtheria, and acellular
pertussis (Tdap) vaccine in adults 19 years and older who have not previously
received Tdap; expanding the indications for pneumococcal polyvalent-23 vaccine
to include all adults with asthma and all smokers; annual seasonal influenza
vaccination for all adults; and booster doses of meningococcal vaccine for adults
with high-risk conditions. It is vital for family physicians to implement a
systematic approach to adult immunization that is patient-, staff-, and physician
focused.
PMID- 22046943
TI - Diagnosis and management of osteomyelitis.
AB - The incidence of chronic osteomyelitis is increasing because of the prevalence of
predisposing conditions such as diabetes mellitus and peripheral vascular
disease. The increased availability of sensitive imaging tests, such as magnetic
resonance imaging and bone scintigraphy, has improved diagnostic accuracy and the
ability to characterize the infection. Plain radiography is a useful initial
investigation to identify alternative diagnoses and potential complications.
Direct sampling of the wound for culture and antimicrobial sensitivity is
essential to target treatment. The increased incidence of methicillin-resistant
Staphylococcus aureus osteomyelitis complicates antibiotic selection. Surgical
debridement is usually necessary in chronic cases. The recurrence rate remains
high despite surgical intervention and long-term antibiotic therapy. Acute
hematogenous osteomyelitis in children typically can be treated with a four-week
course of antibiotics. In adults, the duration of antibiotic treatment for
chronic osteomyelitis is typically several weeks longer. In both situations,
however, empiric antibiotic coverage for S. aureus is indicated.
PMID- 22046944
TI - Osteomyelitis: what you should know.
PMID- 22046945
TI - Bubbles on the skin following renal transplant.
PMID- 22046946
TI - Flaws in clinical reasoning: a common cause of diagnostic error.
PMID- 22046949
TI - E-Z Gold Starter Kit Items Available.
PMID- 22046950
TI - Vehicle head restraint positioning knowledge and behaviours in a sample of Irish
drivers.
AB - A correctly positioned vehicle head restraint (HR) can reduce whiplash injury
risk in collisions, however, HRs are often sub-optimally positioned. The primary
aim of this study was to investigate vehicle HR position and driver knowledge of
correct HR positioning in an Irish population. Secondary aims were to investigate
the associations with driver age, gender and vehicle age. Data collection
involved HR measurement and a driver questionnaire (n = 110). Just 27% of drivers
had optimal HR positioning, while 30% had poor or marginal positioning. Newer
vehicles (<5 years old) had better positioned HR in the horizontal plane (p =
0.036), than older vehicles. Younger drivers (<30 years) were more likely to have
poorer positioning of HR (p = 0.002), than the 30 years or over group. Females
were more likely to have better vertical positioning of their HR (p = 0.003) than
males. Driver knowledge of correct position was variable, and not associated with
actual HR position, with 65% knowing the correct vertical positioning standard
but only 27% identifying the correct horizontal position. Many drivers have
inadequately positioned HR, which needs to be addressed by improved vehicle
design and public education.
PMID- 22046951
TI - Copper-catalyzed tyrosine nitration.
AB - Tyrosine nitration, often observed during neurodegenerative disorders under
nitrative stress, is usually considered to be induced chemically either by nitric
oxide and oxygen forming nitrogen dioxide or by the decomposition of
peroxynitrite. It can also be induced enzymatically by peroxidases or superoxide
dismutases in the presence of both hydrogen peroxide and nitrite forming nitrogen
dioxide and/or peroxynitrite. In this study, the role of cupric ions for
catalyzing tyrosine nitration in the presence of hydrogen peroxide and nitrite,
by a chemical mechanism rather similar to enzymatic pathways where nitrite is
oxidized to form nitrogen dioxide, was investigated by development of a
microreactor also capable of acting as an emitter for electrospray ionization
mass spectrometry analysis. Indeed, cupric ions and peptide-cupric ion complexes
are found to be excellent Fenton catalysts, even better than Fe(III) or heme, for
the formation of (*)OH radicals and/or copper(II)-bound (*)OH radicals from
hydrogen peroxide. These radicals are efficiently scavenged by nitrite anions to
form (*)NO(2) and by tyrosine to form tyrosine radicals, leading to tyrosine
nitration in polypeptides. We also show that cupric ions can catalyze tyrosine
nitration from nitric oxide, oxygen, and hydrogen peroxide as the formation of
tyrosine radicals is increased in the presence of diffusible and/or copper(II)
bound hydroxyl radicals. This study shows that copper has a polyvalent role in
the processes of tyrosine nitration.
PMID- 22046953
TI - Asian-specific total knee system: 5-14 year follow-up study.
AB - BACKGROUND: Knee size and body size differ in Asians compared with Caucasians.
Nevertheless, many total knee arthroplasty (TKA) prostheses used worldwide are
made for Western Caucasian subjects. As a result, an Asian's knee might not fit
these prostheses. We studied the Flexible Nichidai Knee (FNK) system, a new model
of TKA for Asian patients. The purpose of this report is to investigate the
outcomes of this prosthesis retrospectively. METHODS: We investigated 1055
primary TKAs in 595 patients who underwent FNK for osteoarthritis (OA) in Japan
and were followed for > 5 years. The knee score and function score were used for
clinical evaluation. We examined the range of motion (ROM) preoperatively and at
final follow-up and radiographic assessments. In addition, postoperative
complications were investigated. A survivorship analysis was also conducted using
two endpoints: revision for any reason and aseptic failure. RESULTS: 890 knees in
502 patients were available for study (follow-up rate of 96.0%). The mean follow
up term was 8.3 years (range, 5.0-14.1 years). The knee and function score
significantly improved from 41.3 to 90.3 and from 39.1 to 76.2 points,
respectively (p < 0.001). The mean ROM in FNK posterior cruciate retaining (CR)
type and FNK posterior-stabilized (PS) type ameliorated significantly from 107.8
degrees and 95.6 degrees to 110.7 degrees and 110.4 degrees , respectively (p
< 0.01). Ten knees underwent revision surgery (infection in 3 cases, instability
in 2, loosening in 2, and non-union of femoral supracondylar fracture, severe
pain, and recurrent hemarthrosis in 1 each). The survivorship rate was 99.4% (95%
CI, 99.0-99.8) at 5 years (n = 952 patients at risk) and 96.2% (95% CI, 91.9-100)
at 12.5 years (n = 49 patients at risk). CONCLUSION: The FNK prosthesis for
Asians achieved excellent mid- to long-term survivorship and clinical results.
PMID- 22046952
TI - Immunobiotic lactic acid bacteria beneficially regulate immune response triggered
by poly(I:C) in porcine intestinal epithelial cells.
AB - This study analyzed the functional expression of TLR3 in various gastrointestinal
tissues from adult swine and shows that TLR3 is expressed preferentially in
intestinal epithelial cells (IEC), CD172a(+)CD11R1(high) and CD4(+) cells from
ileal Peyer's patches. We characterized the inflammatory immune response
triggered by TLR3 activation in a clonal porcine intestinal epitheliocyte cell
line (PIE cells) and in PIE-immune cell co-cultures, and demonstrated that these
systems are valuable tools to study in vitro the immune response triggered by
TLR3 on IEC and the interaction between IEC and immune cells. In addition, we
selected an immunobiotic lactic acid bacteria strain, Lactobacillus casei
MEP221106, able to beneficially regulate the anti-viral immune response triggered
by poly(I:C) stimulation in PIE cells. Moreover, we deepened our understanding of
the possible mechanisms of immunobiotic action by demonstrating that L. casei
MEP221106 modulates the interaction between IEC and immune cells during the
generation of a TLR3-mediated immune response.
PMID- 22046955
TI - Magnetic manipulation and optical imaging of an active plasmonic single-particle
Fe-Au nanorod.
AB - Superparamagnetic microbeads play an important role in a number of scientific and
biotechnology applications including single-molecule force measurements, affinity
separation, and in vivo and in vitro diagnostics. Magneto-optically active
nanorods composed of single-crystalline Au and polycrystalline Fe segments were
synthesized with diameters of 60 or 295 nm using templated electrodeposition. The
Fe section was magnetically soft and had a saturation magnetization of
approximately 200 emu/g, resulting in a 10-fold increase in magnetization
relative to that iron oxide nanoparticles. The strong plasmonic response of the
Au segment of the rod in both the longitudinal and transverse directions made it
possible to detect the orientation of a single rod in a polarized light
microscope with nanometer resolution. These nanorods provide significantly
improved physical properties over iron oxide superparamagnetic beads, making it
possible to simultaneously manipulate and monitor the orientation of biomolecules
with well-defined forces at the nanometer scale.
PMID- 22046954
TI - Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute
toxicity and initial treatment response.
AB - BACKGROUND AND PURPOSE: To investigate toxicity and efficacy in high-risk
malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2
resected adenoid cystic carcinoma was already improved with a combination of IMRT
and carbon ion boost at only mild side-effects, hence this treatment was also
offered to patients with MSGT and microscopic residual disease (R1) or perineural
spread (Pn+). METHODS: From November 2009, all patients with MSGT treated with
carbon ion therapy were evaluated. Acute side effects were scored according to
CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable.
RESULTS: 103 patients were treated from 11/2009 to 03/2011, median follow-up is 6
months. 60 pts received treatment following R2 resections or as definitive
radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients
received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE
(23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon
ions for re-irradiation. All treatments were completed as planned and generally
well tolerated with no > CTC degrees III toxicity. Rates of CTC degrees III
toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely
resolved at first follow-up.47 patients showed good treatment responses (CR/PR)
according to RECIST. CONCLUSION: Acute toxicity remains low in IMRT with carbon
ion boost also in R1-resected patients and patients undergoing re-irradiation. R2
resected patients showed high rates of treatment response, though follow-up is
too short to assess long-term disease control.
PMID- 22046956
TI - Effects of the distributions of energy or charge transfer rates on spectral hole
burning in pigment-protein complexes at low temperatures.
AB - Effects of the distributions of excitation energy transfer (EET) rates
(homogeneous line widths) on the nonphotochemical (resonant) spectral hole
burning (SHB) processes in photosynthetic chlorophyll-protein complexes (reaction
center [RC] and CP43 antenna of Photosystem II from spinach) are considered. It
is demonstrated that inclusion of such a distribution results in somewhat more
dispersive hole burning kinetics. More importantly, however, inclusion of the EET
rate distributions strongly affects the dependence of the hole width on the
fractional hole depth. Different types of line width distributions have been
explored, including those resulting from Forster type EET between weakly
interacting pigments as well as Gaussian ones, which may be a reasonable
approximation for those resulting, for instance, from so-called extended Forster
models. For Gaussian line width distributions, it is possible to determine the
parameters of both line width and tunneling parameter distributions from SHB data
without a priori knowledge of any of them. Concerning more realistic asymmetric
distributions, we demonstrate, using the simple example of CP43 antenna, that one
can use SHB modeling to estimate electrostatic couplings between pigments and
support or exclude assignment of certain pigment(s) to a particular state.
PMID- 22046957
TI - Congruent genetic structure in the lichen-forming fungus Lobaria pulmonaria and
its green-algal photobiont.
AB - The extent of codispersal of symbionts is one of the key factors shaping genetic
structures of symbiotic organisms. Concordant patterns of genetic structure are
expected in vertically transmitted symbioses, whereas horizontal transmission
generally uncouples genetic structures unless the partners are coadapted. Here,
we compared the genetic structures of mutualists, the lichen-forming fungus
Lobaria pulmonaria and its primary green-algal photobiont, Dictyochloropsis
reticulata. We performed analysis of molecular variance and variogram analysis to
compare genetic structures between symbiosis partners. We simulated the expected
number of multilocus-genotype recurrences to reveal whether the distribution of
multilocus genotypes of either species was concordant with panmixia. Simulations
and tests of linkage disequilibrium provided compelling evidence for the
codispersal of mutualists. To test whether genotype associations between
symbionts were consistent with randomness, as expected under horizontal
transmission, we simulated the recurrence of fungal-algal multilocus genotype
associations expected by chance. Our data showed nonrandom associations of fungal
and algal genotypes. Either vertical transmission or horizontal transmission
coupled with coadaptation between symbiont genotypes may have created these
nonrandom associations. This study is among the first to show codispersal and
highly congruent genetic structures in the partners of a lichen mutualism.
PMID- 22046958
TI - A comprehensive analysis of genes encoding small secreted proteins identifies
candidate effectors in Melampsora larici-populina (poplar leaf rust).
AB - The obligate biotrophic rust fungus Melampsora larici-populina is the most
devastating and widespread pathogen of poplars. Studies over recent years have
identified various small secreted proteins (SSP) from plant biotrophic
filamentous pathogens and have highlighted their role as effectors in host
pathogen interactions. The recent analysis of the M. larici-populina genome
sequence has revealed the presence of 1,184 SSP-encoding genes in this rust
fungus. In the present study, the expression and evolutionary dynamics of these
SSP were investigated to pinpoint the arsenal of putative effectors that could be
involved in the interaction between the rust fungus and poplar. Similarity with
effectors previously described in Melampsora spp., richness in cysteines, and
organization in large families were extensively detailed and discussed. Positive
selection analyses conducted over clusters of paralogous genes revealed fast
evolving candidate effectors. Transcript profiling of selected M. laricipopulina
SSP showed a timely coordinated expression during leaf infection, and the
accumulation of four candidate effectors in distinct rust infection structures
was demonstrated by immunolocalization. This integrated and multifaceted approach
helps to prioritize candidate effector genes for functional studies.
PMID- 22046959
TI - Sclerotinia sclerotiorum gamma-glutamyl transpeptidase (Ss-Ggt1) is required for
regulating glutathione accumulation and development of sclerotia and compound
appressoria.
AB - Transcripts encoding Sclerotinia sclerotiorum gamma-glutamyl transpeptidase (Ss
Ggt1) were found to accumulate specifically during sclerotium, apothecium, and
compound appressorium development in S. sclerotiorum. To determine the
requirement of this protein in these developmental processes, gene deletion
mutants of Ss-ggt1 were generated and five independent homokaryotic DeltaSs-ggt1
mutants were characterized. All deletion mutants overproduced sclerotial initials
that were arrested in further development or eventually produced sclerotia with
aberrant rind layers. During incubation for carpogenic germination, these
sclerotia decayed and failed to produce apothecia. Total glutathione accumulation
was approximately 10-fold higher and H(2)O(2) hyperaccumulated in DeltaSs-ggt1
sclerotia compared with the wild type. Production of compound appressoria was
also negatively affected. On host plants, these mutants exhibited a defect in
infection efficiency and a delay in initial symptom development unless the host
tissue was wounded prior to inoculation. These results suggest that Ss-Ggt1 is
the primary enzyme involved in glutathione recycling during these key
developmental stages of the S. sclerotiorum life cycle but Ss-Ggt1 is not
required for host colonization and symptom development. The accumulation of
oxidized glutathione is hypothesized to negatively impact these developmental
processes by disrupting the dynamic redox environment associated with
multicellular development.
PMID- 22046960
TI - N-terminal motifs in some plant disease resistance proteins function in membrane
attachment and contribute to disease resistance.
AB - To investigate the role of N-terminal domains of plant disease resistance
proteins in membrane targeting, the N termini of a number of Arabidopsis and flax
disease resistance proteins were fused to green fluorescent protein (GFP) and the
fusion proteins localized in planta using confocal microscopy. The N termini of
the Arabidopsis RPP1-WsB and RPS5 resistance proteins and the PBS1 protein, which
is required for RPS5 resistance, targeted GFP to the plasma membrane, and
mutation of predicted myristoylation and potential palmitoylation sites resulted
in a shift to nucleocytosolic localization. The N-terminal domain of the membrane
attached Arabidopsis RPS2 resistance protein was targeted incompletely to the
plasma membrane. In contrast, the N-terminal domains of the Arabidopsis RPP1-WsA
and flax L6 and M resistance proteins, which carry predicted signal anchors, were
targeted to the endomembrane system, RPP1-WsA to the endoplasmic reticulum and
the Golgi apparatus, L6 to the Golgi apparatus, and M to the tonoplast. Full
length L6 was also targeted to the Golgi apparatus. Site-directed mutagenesis of
six nonconserved amino acid residues in the signal anchor domains of L6 and M was
used to change the localization of the L6 N-terminal fusion protein to that of M
and vice versa, showing that these residues control the targeting specificity of
the signal anchor. Replacement of the signal anchor domain of L6 by that of M did
not affect L6 protein accumulation or resistance against flax rust expressing
AvrL567 but removal of the signal anchor domain reduced L6 protein accumulation
and L6 resistance, suggesting that membrane attachment is required to stabilize
the L6 protein.
PMID- 22046961
TI - Efficacy and safety of budesonide/formoterol via a dry powder inhaler in Chinese
patients with chronic obstructive pulmonary disease.
AB - OBJECTIVE: To evaluate the efficacy and safety of budesonide (BUD)/formoterol
(FORM) compared with BUD, both administered by way of a dry powder inhaler
(Turbuhaler * ). * Turbuhaler is a registered trade name of AstraZeneca,
Sodertalje, Sweden. METHODS: This was a 6-month, multicenter, randomized,
parallel-group, double-blind, double-dummy design study (NCT 00421122). Patients
were randomized to either BUD/FORM 160/4.5 MUg, two inhalations twice daily, or
BUD 200 MUg, two inhalations twice daily. Improvement of lung function, daily
symptoms, reliever use and health-related quality-of-life (St George's
Respiratory Questionnaire [SGRQ] score) were compared between the two treatment
groups. RESULTS: A total of 308 patients with moderate to very severe COPD from
12 centers in China were randomized to BUD/FORM (n = 156) or BUD (n = 152). The
primary endpoint, 1-hour post-dose forced expiratory volume in 1 second (FEV1),
in the BUD/FORM group improved by 0.18 L (from 0.83 L at baseline to 1.01 L) and
this was significantly better (p < 0.001) than the small increase (0.03 L)
observed in the BUD group after 24 weeks' treatment. Increases in pre-dose and 15
min post-dose FEV(1) together with 1-hour post-dose forced vital capacity were
also significantly larger with BUD/FORM than BUD (p < 0.001 for all). Compared
with BUD alone, BUD/FORM improved COPD total symptom scores (-1.04 +/- 0.16 vs.
0.55 +/- 0.17; p = 0.03), reduced reliever use (-0.85 +/- 0.16 puffs/day vs.
0.31 +/- 0.16 puffs/day; p = 0.012) and improved health-related quality-of-life
(mean change of total SGRQ score -4.5 points (p = 0.0182). Overall, both
treatments were well tolerated. CONCLUSIONS: In Chinese patients with moderate to
very severe COPD, fixed combination treatment with BUD/FORM resulted in
clinically meaningful improvements in lung function, health-related quality-of
life, COPD symptoms and a reduction in reliever use, compared with BUD alone and
both treatments were well tolerated. Treatment of BUD/FORM for milder patients
with COPD and head to head comparison of Chinese and Caucasians in future studies
will be helpful to expand upon the findings of the current clinical trial.
PMID- 22046963
TI - Photorelease of primary aliphatic and aromatic amines by visible-light-induced
electron transfer.
AB - Visible-light-absorbing tris(bipyridyl)ruthenium(II) has been used to mediate
electron transfer to N-methylpicolinium carbamates that undergo C-O bond
fragmentation followed by spontaneous carbon dioxide release to give free amines.
Release of several aliphatic and aromatic primary amines has been demonstrated
under mild conditions using visible light.
PMID- 22046962
TI - Self-assembling, protein-based intracellular bacterial organelles: emerging
vehicles for encapsulating, targeting and delivering therapeutical cargoes.
AB - Many bacterial species contain intracellular nano- and micro-compartments
consisting of self-assembling proteins that form protein-only shells. These
structures are built up by combinations of a reduced number of repeated elements,
from 60 repeated copies of one unique structural element self-assembled in
encapsulins of 24 nm to 10,000-20,000 copies of a few protein species assembled
in a organelle of around 100-150 nm in cross-section. However, this apparent
simplicity does not correspond to the structural and functional sophistication of
some of these organelles. They package, by not yet definitely solved mechanisms,
one or more enzymes involved in specific metabolic pathways, confining such
reactions and sequestering or increasing the inner concentration of unstable,
toxics or volatile intermediate metabolites. From a biotechnological point of
view, we can use the self assembling properties of these particles for directing
shell assembling and enzyme packaging, mimicking nature to design new
applications in biotechnology. Upon appropriate engineering of the building
blocks, they could act as a new family of self-assembled, protein-based vehicles
in Nanomedicine to encapsulate, target and deliver therapeutic cargoes to
specific cell types and/or tissues. This would provide a new, intriguing platform
of microbial origin for drug delivery.
PMID- 22046964
TI - Fever and associated clinical haematologic and blood biochemical changes in the
goat and other animal species.
AB - Summary Acute febrile diseases are characterized by specific and non-specific
symptoms. The non-specific responses are presented under the headings: fever,
inflammation and pain, experimental models for investigating febrile reactions,
haematologic changes, blood biochemical changes, cardiovascular effects, changes
in gastric function, and the effects of fever upon pharmacokinetics of drugs. It
was the purpose of this review to describe present concepts of thermoregulation
and fever, the associated reactions produced by bacterial pyrogens and the
mechanisms of these reactions. The available data illustrate, that many questions
have not yet been clearly answered. However, the entire field of research
involving endogenous substances, such as interleukin-1, is now moving ahead with
great speed. Furthermore, there is some evidence which suggests that fever and
the associated lower plasma zinc and iron levels act together as a co-ordinated
non-specific host defence mechanism. Since experimental fever has a distinct
effect upon the pharmacokinetics of drugs, more attention should be given to this
aspect.
PMID- 22046966
TI - Ficus platyphylla promotes fertility in female Rattus norvegicus Wistar strain: a
preliminary study.
AB - BACKGROUND: Ficus platyphylla Delile (family-Moracea) commonly called gutta
percha tree is a deciduous plant found in savannah areas. It grows widely in the
Northern part of Nigeria, up to 60 ft. high and is known as 'gamji' by the
Hausas. The seeds, bark and leaves have been used traditionally in combination to
promote fertility. Scientifically, the plant has been shown to have analgesic,
anti-inflammatory and CNS effects. The present study was to validate the use of
this plant to promote fertility in female Rattus norvegicus Wistar strain using
various fertility parameters. METHODS: Female Rattus norvegicus Wistar strain
weighing between 150-180 g were randomly selected and divided into two major
groups. Each group was subdivided into 5 treatment groups of 100, 200, 400 mg/kg
BW of aqueous extract of F. platyphylla and a control group of 5 ml/kg of
distilled water. A positive control of clomiphene citrate was used. Treatment of
the first group was discontinued after 15 days prior to mating (pre-mating
treatment group), while the other was treated continuously till delivery
(continuous treatment group). At the 10th day, females were sacrificed and
implantation sites were checked and embryos counted. Upon delivery, litter sizes
were determined and the pups weighed and checked for deformities. Other
reproductive indices were calculated. Data were analyzed by one-way analysis of
variance and students T-test. Proportions were analysed by Chi square.
Statistical evaluations were performed using STATS programs and Graphpad prism,
and a difference was considered statistically significant at P < 0.05. RESULTS:
There was a significant reduction in the percentage post implantation losses of
both the pre-treatment and the continuous treatment groups when compared to their
distil water controls. The litter size of the pre-treatment group was similar to
the distil water group while at 400 mg/kg, the continuous treatment group showed
an increase in the litter size similar to that of the clomiphene group. There
were no observed external deformities in the pups. CONCLUSIONS: Administration of
aqueous extract of F. platyphylla promotes fertility by reducing post
implantation loss and by increasing litter size in female Rattus norvegicus
Wistar strain.
PMID- 22046967
TI - Risk of infections in bronchiectasis during disease-modifying treatment and
biologics for rheumatic diseases.
AB - BACKGROUND: Bronchiectasis is frequently associated (up to 30%) with chronic
inflammatory rheumatic diseases and leads to lower respiratory tract infections.
Data are lacking on the risk of lower respiratory tract infections in patients
treated with biologic agents. METHODS: Monocenter, retrospective systematic study
of all patients with a chronic inflammatory rheumatic disease and concomitant
bronchiectasis, seen between 2000 and 2009. Univariate and multivariate analyses
were performed to evidence predictive factors of the number of infectious
respiratory events. RESULTS: 47 patients were included (mean age 64.1+/-9.1
years, 33 (70.2%) women), with a mean follow-up per patient of 4.3+/-3.1 years.
Rheumatoid arthritis was the main rheumatic disease (90.1%). The mean number of
infectious events was 0.8+/-1.0 event per patient-year. The factors predicting
infections were the type of treatment (biologic vs. non biologic disease
modifying treatments), with an odds ratio of 8.7 (95% confidence interval: 1.7
43.4) and sputum colonization by any bacteria (odds ratio 7.4, 2.0-26.8). In
multivariate analysis, both factors were independently predictive of infections.
CONCLUSION: Lower respiratory tract infectious events are frequent among patients
receiving biologics for chronic inflammatory rheumatic disease associated with
bronchiectasis. Biologic treatment and pre-existing sputum colonization are
independent risk factors of infection occurrence.
PMID- 22046968
TI - Prevention of diabetes complications in developing countries: time to intensify
self-management education.
AB - The IDF report has indicated that about 80% of four million diabetes-related
deaths that occur every year comes from the developing world. The IDF report
suggests the need to focus more on preventing diabetes complications in poor
countries. Thus, considering the economic constraints in combating the explosion
of diabetes complications in the developing regions of the world, it appears that
exploring culturally adaptable educational intervention programmes for specific
regions would be the appropriate strategy. We believe that diabetes-related
deaths could be reduced in developing countries through intensified diabetes self
management education.
PMID- 22046969
TI - A rapid microbioassay for discovery of antagonistic bacteria for Phytophthora
parasitica var. nicotianae.
AB - A simple, rapid, small-scale microbioassay for infection of tobacco seedlings by
Phytophthora parasitica var. nicotianae was developed here. This assay uses
tobacco seedlings cultivated in petri dishes for a standardized method for
quantitation of initial zoospore inocula and high-throughput screening of
antagonistic bacteria. Zoospore inocula between 10(2) to 10(5) spores per petri
dish were inoculated on 14-day-old tobacco seedlings for the susceptibility test.
The optimum inocula was established to be ten thousand zoospores. One hundred and
fifty pure culture bacteria with different pigments, growth rates, and
morphologies were isolated from rhizosphere soil of tobacco and screened for
protective ability against tobacco black shank. Fifteen bacteria presented high
activity against P. parasitica on tobacco seedlings. They were identified by
Biolog GEN III MicroPlate and distributed as Bacillus amyloliquefaciens, B.
licheniformis, Paenibacillus pabuli, B. atrophaeus, B. subtilis, B. pumilus, and
B. endophyticus, respectively. Four antagonists chosen randomly from the 15
bacteria all exhibited the same 100% protective activity in planta as that in the
petri dishes. This microassay proved to be a rapid, reproducible, and efficient
method for screening of potential biological agents or microorganisms and may be
useful for studying mechanisms of infection and control of Phytophthora spp.
under hydroponic conditions.
PMID- 22046970
TI - Differential expression of CD300a/c on human TH1 and TH17 cells.
AB - BACKGROUND: Human memory CD4+ T cells can be either CD300a/c+ or CD300a/c- and
subsequent analyses showed that CD4+ effector memory T (T(EM)) cells are mostly
CD300a/c+, whereas CD4+ central memory T (T(CM)) cells have similar frequencies
of CD300a/c+ and CD300a/c- cells. RESULTS: Extensive phenotypical and functional
characterization showed that in both T(CM) and T(EM) cells, the CD300a/c+ subset
contained a higher number of TH1 (IFN-gamma producing) cells. Alternatively, TH17
(IL-17a producing) cells tend to be CD300a/c-, especially in the T(EM) subset.
Further characterization of the IL-17a+ cells showed that cells that produce only
this cytokine are mostly CD300a/c-, while cells that produce IL-17a in
combination with other cytokines, especially IFN-gamma, are mostly CD300a/c+,
indicating that the expression of this receptor is associated with cells that
produce IFN-gamma. Co-ligation of the TCR and CD300a/c in CD4+ T cells inhibited
Ca2+ mobilization evoked by TCR ligation alone and modulated IFN-gamma production
on TH1 polarized cells. CONCLUSION: We conclude that the CD300a/c receptors are
differentially expressed on human TH1 and TH17 cells and that their ligation is
capable of modulating TCR mediated signals.
PMID- 22046971
TI - Belinostat: clinical applications in solid tumors and lymphoma.
AB - INTRODUCTION: Histone deacetylase (HDAC) inhibitors have recently emerged as a
novel and active class of anticancer agents. Belinostat is one member of the
class that has been tested as a single agent and in combination with other
chemotherapies and biological agents in the treatment of solid tumors and
lymphoma. AREAS COVERED: A literature search of pre-clinical and clinical studies
of belinostat was performed. The data from these studies were analysed to
summarise the progress of belinostat from Phase I to a current pivotal trial in
peripheral T-cell lymphoma. The parallel development of appropriate biomarker
analysis is also discussed. EXPERT OPINION: Belinostat has demonstrated
significant clinical activity in T-cell lymphomas. Although its activity as a
single agent in solid tumors has been less compelling, the emerging results from
combination trials are promising. However, the basis for the activity of
belinostat, like that of other HDAC inhibitors, remains to be truly defined and
the identification of predictive and prognostic biomarkers of activity should be
established to further progress the development of this compound.
PMID- 22046972
TI - Identifying and explicating variation among friends with benefits relationships.
AB - This two-study report identifies and validates a typology containing seven types
of "friends with benefits relationships" (FWBRs). Study 1 asked heterosexual
students to define the term FWBR and to describe their experience with the
relationship type. Qualitative analysis of these data identified seven types of
FWBRs (true friends, network opportunism, just sex, three types of transition in
[successful, failed, and unintentional], and transition out). Study 2
quantitatively differentiates these relationship types in the amount of nonsexual
interaction, strength of the friendship at the first sexual interaction, and
history of romantic relationships with the FWBR partner (before the FWBR, after
it, or both). Results from both studies clearly suggest that FWBRs represent a
diverse set of relationship formulations where both the benefits (i.e., repeated
sexual contact) and the friends (i.e., relationship between partners) vary
widely. In many cases, FWBRs represent a desire for, or an attempt at, shifting
the relationship from friends to a romantic partnership. Other implications are
discussed, as are limitations and directions for future research. The diverse
nature of FWBRs provides challenges for researchers that likely require multiple
methods and theoretical frames.
PMID- 22046973
TI - The use of pharmacotherapy in pregnancies with suspected diabetic fetopathy.
AB - OBJECTIVE: To review the evidence supporting incorporation of sonographic fetal
measurements in deciding whether or not to add insulin to diet therapy
independent of maternal glucose measures for women who have gestational diabetes.
METHODS: A literature search was conducted for studies incorporating sonographic
estimates of fetal measures in the selection of treatment. Only randomized
controlled trials were selected for review. RESULTS: Four studies meeting
selection criteria were identified. Methods of randomization, sonographic
measurements used to indicate the addition of insulin for treatment, and clinical
endpoints differed somewhat from study to study. Most studies reported a decrease
in large neonates among women whose insulin treatment was indicated by
ultrasound. In each study the targeted glucose values for patients treated with
insulin based on sonographic measurements were lower than for those treated
exclusively with diet. CONCLUSIONS: Available evidence suggests a benefit in
reducing the incidence of large birth weight babies to mothers who have
gestational diabetes by utilizing designated sonographic parameters in the
decision to add pharmacotherapy in addition to using glucose thresholds. To
support these findings, studies are needed in which glycemic targets comparing
groups whose insulin treatment is based on maternal glucose results with those
based on ultrasound measurements are identical.
PMID- 22046974
TI - Evaluation of biomarkers of oxidative stress and antioxidant capacity in the cord
blood of preterm low birth weight neonates.
AB - OBJECTIVE: The objective of the study is to investigate the association between
oxidative stress markers and enzymatic / non-enzymatic antioxidants (marker of
the resistance in body to oxidative damage) in the cord blood of preterm low
birth weight (LBW) neonates. METHODS: Malondialdehyde (MDA), carbonyl proteins,
total antioxidant capacity and Vitamin A, E and C levels in the cord blood were
determined by spectrophotometry. RESULTS: Increased lipid peroxidation, protein
oxidation with decreased values of vitamin A, E, C and total antioxidant capacity
were observed in the preterm LBW newborns. Observations of negative correlation
between MDA and protein carbonyl with antioxidants vitamin A, E and C and total
antioxidant status points towards the existence of oxidative stress in the
preterm LBW newborns. CONCLUSIONS: Poor fetal growth affects the development of
antioxidant defenses of preterm LBW babies, predisposing them to higher oxidative
stress, which in turn may partly account for increased morbidity and mortality in
these infants. The presence of an association between oxidative stress biomarkers
and enzymatic /non-enzymatic antioxidants in the cord blood of preterm LBW
neonates suggest that increased oxidative stress may be the result of changes in
the levels of certain enzymatic and non-enzymatic antioxidants due to the cause
or the effect of oxidative damage occurring at the molecular level.
PMID- 22046975
TI - Comment on: guidelines for the management of spontaneous preterm labor:
identification of spontaneous preterm labor, diagnosis of preterm premature
rupture of membranes and preventive tools for preterm birth.
PMID- 22046976
TI - Predictive factors of perinatal mortality in transfused fetuses due to maternal
alloimmunization: what really matters?
AB - INTRODUCTION: Alloimmunization is the main cause of fetal anemia. There are not
many consistent analyses associating antenatal parameters to perinatal mortality
in transfused fetuses due to maternal alloimmunization. The study aimed to
determine the prognostic variables related to perinatal death. MATERIAL AND
METHODS: A cohort study analyzed 128 fetuses treated with intrauterine
transfusion (IUT), until the early neonatal period. Perinatal mortality was
associated with prognostic conditions related to prematurity, severity of fetal
anemia and IUT procedure by univariated logistic regression. Multiple logistic
regression was used to compute the odds ratio (OR) for adjusting the hemoglobin
deficit at the last IUT, gestational age at birth, complications of IUT,
antenatal corticosteroid and hydrops. RESULTS: Perinatal mortality rate found in
this study was 18.1%. The hemoglobin deficit at the last IUT (OR: 1.26, 95% CI:
1.04-1.53), gestational age at birth (OR: 0.53, 95% CI: 0.38-0.74) and the
presence of transfusional complications (OR: 5.43, 95% CI: 142-20.76) were
significant in predicting fetal death. CONCLUSION: Perinatal mortality prediction
in transfused fetuses is not associated only to severity of anemia, but also to
the risks of IUT and prematurity.
PMID- 22046977
TI - Maternal serum interleukin-6 levels predict impending funisitis in preterm
premature rupture of membranes after completion of antibiotics.
AB - OBJECTIVE: To determine if maternal serum interleukin-6 (IL-6) levels remain
predictive of funisitis after completion of antibiotic administration in preterm
premature rupture of membranes (PPROM). METHODS: A secondary analysis of a
prospective cohort study. Daily blood samples obtained from PPROM subjects were
analyzed for IL-6 by enzyme-linked immunosorbent assay. Subjects (N = 39)
delivered >7 days post admission and were divided into those with and without
funisitis. Data were analyzed using Mann-Whitney U test. RESULTS: Maternal serum
IL-6 levels obtained 24-48 hours and 48-72 hours before delivery are elevated in
PPROM subjects with funisitis compared to those without funisitis (6.3 vs. 2.7
pg/ml, P < 0.03; 6.1 vs. 1.7 pg/ml, P < 0.02). Receiver operator characteristic
curve revealed an IL-6 level of 1.98 pg/ml had sensitivity of 86.7%, specificity
of 46.7%, positive predictive value of 61.9% and negative predictive value of
77.8%. CONCLUSION: This data suggests that maternal serum IL-6 levels continue to
be predictive of PPROM subjects destined to develop funisitis after completion of
antibiotics.
PMID- 22046978
TI - Maternal N-acetyl-cysteine (NAC) protects the rat fetal brain from inflammatory
cytokine responses to lipopolysaccharide (LPS).
AB - OBJECTIVE: Inflammatory cytokines, play a central role in the genesis of preterm
parturition and fetal brain injury. Lipopolysaccharide (LPS) may activate
cytokine pathways via induction of oxidative stress pathways. We hypothesized
that enhanced maternal antioxidant activity may blunt fetal brain inflammatory
responses to maternal LPS injection in pregnant rats. METHODS: Pregnant Sprague
Dawley rats at 18 and 20 days gestation received intraperitoneal (ip) LPS
injection and pre- and post-treatment with the antioxidant N-acetyl-cysteine
(NAC) or saline. Six hours after the LPS injection, rats were sacrificed,
interleukin (IL)-6 and IL-10 mRNA expression in the fetal brains was determined
by real time polymerase chain reaction. RESULTS: Maternal ip LPS induced
significant increase in fetal brain IL-6 mRNA expression at E18 (3.1 +/- 0.6 vs
1.0 +/- 0.10 AU) and E20 (29.01 + 13.06 vs 0.95 + 0.05 AU; p < 0.05) compared to
Control, only at E20 maternal LPS induced increase in fetal brain IL-10 compared
to control. NAC administered prior to and after LPS significantly reduced fetal
brain IL-6 at E18 and E20 and IL-10 at E20. CONCLUSION: Maternal NAC can protect
the fetal brain from inflammatory cytokine responses to maternal LPS injection.
These results suggest that NAC may potentially protect fetus from inflammation
associated brain injury and potential long term sequelae.
PMID- 22046980
TI - Errata.
PMID- 22046982
TI - We Did It Our Way.
PMID- 22046979
TI - A review of the responses of two- and three-dimensional engineered tissues to
electric fields.
AB - The application of external biophysical signals is one approach to tissue
engineering that is explored less often than more traditional additions of
exogenous biochemical and chemical factors to direct cell and tissue outcomes.
The study of bioelectromagnetism and the field of electrotherapeutics have
evolved over the years, and we review biocompatible electric stimulation devices
and their successful application to tissue growth. Specifically, information on
capacitively coupled alternating current, inductively coupled alternating
current, and direct current devices is described. Cell and tissue responses from
the application of these devices, including two- and three-dimensional in vitro
studies and in vivo studies, are reviewed with regard to cell proliferation,
adhesion, differentiation, morphology, and migration and tissue function. The
current understanding of cellular mechanisms related to electric stimulation is
detailed. The advantages of electric stimulation are compared with those pf other
techniques, and areas in which electric fields are used as an adjuvant therapy
for healing and regeneration are discussed.
PMID- 22046983
TI - Announcement of the 2009 Paffenbarger Student Research Fellowship Award.
PMID- 22046984
TI - 2010 Ralph Phillips Student Research Award Request for Applications.
PMID- 22046986
TI - 39(th) Annual Meeting of the Academy of Operative Dentistry: 24-26 February 2010,
Fairmont Hotel, Chicago, IL.
PMID- 22046985
TI - E-Z Gold Starter Kit Items Available.
PMID- 22046987
TI - Psychological adaptation of Moroccan and Ecuadorean immigrant adolescents in
Spain.
AB - In adapting to the host society, immigrant adolescents may have problems
negotiating the challenges of acculturation. The factors that promote and those
that hamper psychological adaptation may not play the same role in all ethnic
groups. Our study focuses on psychological adaptation of two main immigrant
groups in Spain that differ in cultural distance to the host society and level of
societal acceptance: adolescents of Moroccan and Ecuadorean origin. Our findings
show, first, that mainstream cultural orientation is positively related to
psychological adaptation, whereas perceived ethnic discrimination is negatively
associated with adaptation. Second, the relationship between ethnic cultural
orientation and psychological adaptation and between length of residence in Spain
and adaptation is stronger for the Moroccan youth than for their Ecuadorean
peers. Theoretical and practical implications of these results are discussed.
This manuscript was prepared and written while the first author was affiliated to
the University of Cordoba in Spain and financially supported by the Spanish
Ministry of Science and Innovation within the framework of a National Program of
Human Recourses' Mobility (I+D+I 2008-2011). Data collection was financially
supported by the Spanish Ministry of Science and Technology (I+D BSO2003-09222).
PMID- 22046988
TI - Languages on the screen: is film comprehension related to the viewers' fluency
level and to the language in the subtitles?
AB - This research aimed at studying the role of subtitling in film comprehension. It
focused on the languages in which the subtitles are written and on the
participants' fluency levels in the languages presented in the film. In a
preliminary part of the study, the most salient visual and dialogue elements of a
short sequence of an English film were extracted by the means of a free recall
task after showing two versions of the film (first a silent, then a dubbed-into
French version) to native French speakers. This visual and dialogue information
was used in the setting of a questionnaire concerning the understanding of the
film presented in the main part of the study, in which other French native
speakers with beginner, intermediate, or advanced fluency levels in English were
shown one of three versions of the film used in the preliminary part.
Respectively, these versions had no subtitles or they included either English or
French subtitles. The results indicate a global interaction between all three
factors in this study: For the beginners, visual processing dropped from the
version without subtitles to that with English subtitles, and even more so if
French subtitles were provided, whereas the effect of film version on dialogue
comprehension was the reverse. The advanced participants achieved higher
comprehension for both types of information with the version without subtitles,
and dialogue information processing was always better than visual information
processing. The intermediate group similarly processed dialogues in a better way
than visual information, but was not affected by film version. These results
imply that, depending on the viewers' fluency levels, the language of subtitles
can have different effects on movie information processing.
PMID- 22046989
TI - Aspirations and wellbeing in Romanian and US undergraduates.
AB - Updating cross-cultural research of the past decade on the relationship between
life aspirations and wellbeing, we compared Romanian (N=69) and US (N=64)
undergraduates on the contribution of the importance and likelihood of attaining
intrinsic and extrinsic aspirations to psychological maladjustment and life
satisfaction, and on the qualitative meaning they assign to financial success.
Similarly to prior studies, we found that extrinsic and intrinsic aspirations
tended to be either negatively or positively correlated with life satisfaction,
respectively; however, wealth predicted life satisfaction for Romanian students.
Unlike previous research, we found generally negative relationships between
intrinsic aspirations and psychological maladjustment. Although there were no
differences between Romanian and US undergraduates on extrinsic and intrinsic
orientation, on the overall importance of attaining aspirations, or on specific
extrinsic and intrinsic aspirations, Romanian students expressed weaker
expectations of fulfilling intrinsic aspirations than did US students. Finally,
the groups produced similar rankings of aspirations and assigned similar meaning
to financial success. The results favored a social cognitive rather than a self
determination model of psychological wellbeing in that expectations for attaining
aspirations were more often predictive of life satisfaction than were their
content. We interpret these findings and their convergence and departure from
earlier research in terms of political economic, demographic, and cultural
factors. We encourage future cross-cultural investigations of the social
construction of aspirations, subsidiation of seemingly contradictory aspirations
to each other, and cognitive and ecological mediation of the complex relationship
of aspirations to psychological functioning.
PMID- 22046990
TI - The effects of mortality salience on escalation of commitment.
AB - Based on propositions derived from terror management theory (TMT), the current
study proposes that people who are reminded of their mortality exhibit a higher
degree of self-justification behavior to maintain their self-esteem. For this
reason, they could be expected to stick with their previous decisions and invest
an increasing amount of resources in those decisions, despite the fact that
negative feedback has clearly indicated that they might be on a course toward
failure (i.e., "escalation of commitment"). Our experiment showed that people who
were reminded of their mortality were more likely to escalate their level of
commitment by maintaining their current course of action. Two imaginary scenarios
were tested. One of the scenarios involved deciding whether to send additional
troops into the battlefield when previous attempts had failed; the other involved
deciding whether to continue developing an anti-radar fighter plane when the
enemy had already developed a device to detect it. The results supported our
hypothesis that mortality salience increases the tendency to escalate one's level
of commitment.
PMID- 22046991
TI - Taiwanese adolescent cognitive autonomy and identity development: the
relationship of situational and agential factors.
AB - Taiwanese professionals have adopted information about adolescent psychosocial
development from Western societies. However, scholars know little about whether
they have properly applied the models to both rural and urban youth. The purpose
of this study was to examine the development of cognitive autonomy and ego
identity in Taiwanese adolescents from Taipei City and surrounding rural
counties. We controlled for gender and examined both situational (residential
location, family income, and school type) and agential factors (culture value
affiliation, attachment, and resiliency) to determine the extent to which each
predicted psychosocial developmental outcomes. Among all the factors in this
study, resiliency had the most distinctive relationship with adolescent
psychosocial development. Each factor successfully predicted specific aspects of
psychosocial development for these youth. We conclude with a discussion of the
utility of using Western models of development.
PMID- 22046992
TI - Perceived discrimination, social connectedness, and other predictors of
adjustment difficulties among Turkish international students.
AB - This study examined the role of perceived discrimination, social connectedness,
age, gender, years of study in the US, English language competency, and social
contact patterns on adjustment difficulties among a sample of 229 Turkish
international students studying in the United States. Findings indicated that
students who reported higher levels of social connectedness, lower levels of
perceived discrimination, more years of study in the US, and higher levels of
English language competency reported lower levels of adjustment difficulties.
Other results showed that (lack of) social connectedness and perceived
discrimination were predictors of adjustment difficulties. In addition, results
indicated that students who socialized with individuals from the US had lower
levels of adjustment difficulties than did those who socialized with coculture
members. Implications are discussed and suggestions for interventions are
provided.
PMID- 22046993
TI - The effects of functional group counseling on inspiring low-achieving students'
self-worth and self-efficacy in Taiwan.
AB - In this study, we investigated the effects of functional group counseling on
inspiring low achievers' self-worth and self-efficacy in Taiwan. Forty-three 10th
grade low-achieving students volunteered as the Experimental Group to join a 24
week intervention, which integrated and utilized functional group counseling;
another 51 10th grade low-achieving students volunteered to be Comparison Group
I. In addition, 43 10th grade moderate or high academic achieving students
volunteered to be Comparison Group II. All participants completed the Vocational
School Student Questionnaire at the beginning and end of this study to measure
their self-worth and self-efficacy. In addition, six target students (two boys
and four girls) with the lowest total scores on self-worth or self-efficacy in
the pretest were selected from the Experimental Group to be interviewed at the
end of the intervention and observed weekly. Analyses of variance, analyses of
covariance, and paired t-tests assessed the similarity and differences among
groups. The initial findings were as follows: Experimental group students had
significantly higher scores on self-efficacy and self-worth than both Comparison
Group I and Group II students and functional group counseling was shown to
significantly affect the low-achieving students. Qualitative results from
interviews and observations were used for triangulation and consolidation of
quantitative results. Implications of the study included the recommended use of
functional group counseling with low-achieving students.
PMID- 22046994
TI - The effect of achievement goals on enjoyment, effort, satisfaction and
performance.
AB - This study examined the effect of achievement goals and achievement emotions on
sport satisfaction, performance and effort among competitive athletes.
Participants were 200 athletes. Structural equation modeling was used to test the
indirect effect of mastery-approach goals on satisfaction with sport experience
and performance, the direct effect of mastery-approach goals on enjoyment and
effort, the direct effect of performance-approach and performance-avoidance goals
on performance, and the direct effect of mastery-avoidance goals on effort.
Results showed a positive direct effect of mastery-approach goals on enjoyment
and an indirect effect, through enjoyment, on satisfaction, performance, and
effort. We did not find support for the hypothesized effect of performance
approach or performance-avoidance goals on performance. The applied implications
of endorsing mastery-approach goals are discussed.
PMID- 22046995
TI - Motivation and social contexts: a crossnational pilot study of achievement,
power, and affiliation motives.
AB - Previous research suggests that there is a relationship between social contexts
(e.g., economic growth, engagement in wars) and motives within populations. In
particular, high achievement motive is associated with subsequent economic
growth, which in turn increases power motive. Increased national achievement and
power motives have been argued to precede social changes that lead to decreased
affiliation motives, and engagement in wars. The present study aimed to examine
differences in achievement, power, and affiliation motives between 266 college
students in China (a nation with sustained high economic growth) and 255 college
students in the USA (a nation with previously strong but now slowing economic
growth, and engaged in war). Analysis of personal strivings suggested that
Chinese college students showed significantly higher levels of achievement motive
than the American college students, but American college students showed
significantly higher levels of affiliation motive than Chinese college students.
Overall, males exhibited higher achievement motivation than females. No
significant interaction effects were found for gender by location for any of the
three motives. The findings are discussed in relation to previous research.
PMID- 22046996
TI - Cultural differences in athlete attributions for success and failure: the sports
pages revisited.
AB - Self-serving biases in attribution, while found with relative consistency in
research with Western samples, have rarely been found in Japanese samples
typically recruited for research. However, research conducted with Japanese
participants to date has tended to use forced-choice and/or reactive paradigms,
with school or university students, focusing mainly on academic performance or
arbitrary and/or researcher-selected tasks. This archival study explored whether
self-serving attributional biases would be shown in the real-life attributions
for sporting performance made by elite Olympic athletes from Japan and Australia.
Attributions (N = 216) were extracted from the sports pages of Japanese and
Australian newspapers and rated by Australian judges for locus and
controllability. It was hypothesized that Australian, but not Japanese, athletes
would show self-serving biases such that they attributed wins to causes more
internal and controllable than the causes to which they attributed losses.
Contrary to predictions, self-serving biases were shown to at least some extent
by athletes of both nationalities. Both Australian and Japanese men attributed
wins to causes more internal than those to which they attributed losses. Women,
however, attributed wins and losses to causes that did not differ significantly
in terms of locus. All athletes tended to attribute wins to causes that were more
controllable than the causes to which losses were attributed. Results are
inconsistent with a large body of research suggesting that Japanese do not show
self-serving biases in attribution, and are discussed in the light of differences
in methodology, context, and participants that may have contributed to these
effects.
PMID- 22046997
TI - Affective responses to movie posters: differences between adolescents and young
adults.
AB - Although the link between cognition and affect in the advertising context has
been demonstrated in several studies, no research to date has considered
adolescents' affective responses to movie posters and their attitudes to negative
and positive images. A 2 (between subjects) * 4 (within subjects) mixed-factorial
experiment design comprising two groups of subjects (80 adolescents and 80 young
adults) and four advertising stimuli (two highly positive images and two highly
negative images) was used to test the differences in the subjects' attitudes to
advertising, positive and negative affect, and viewing intentions. Although the
adolescents, compared to the young adults, did not appear to have significantly
stronger attitudes to emotional advertisements (ads), they showed a similar level
of intensity of affective response when exposed to negative and positive images.
PMID- 22046998
TI - Gender and work-family conflict: testing the rational model and the gender role
expectations model in the Spanish cultural context.
AB - Gutek, Searle, and Klepa (1991) proposed two models to explain the gender
differences in work-family conflict: the rational model and the gender role
expectations model. Both models have mostly been tested on American and Canadian
samples, and have obtained partial support. Given the cultural differences
between North American countries and Spain, we should question whether the two
models are equally applicable to Spanish society or whether one of them captures
Spanish men and women's experience of work-family conflict better than the other.
So, the aim of this study is to test which of the models better explains the
gender differences in work-family conflict in the Spanish cultural context (or
if, indeed, the two models apply equally well). Given the typical cultural
dimensions of Spanish society, we expected to find greater support for the gender
role expectations model than for the rational model. However, the results
obtained in this study indicated that, while the rational model can explain the
gender differences that were found, the gender role expectations model cannot
capture Spanish people's work-family conflict experiences. The results are
interpreted in terms of cultural dimensions characteristic of the Spanish
context.
PMID- 22046999
TI - Posttraumatic stress and worry as mediators and moderators between political
stressors and emotional and behavioral disorders in Palestinian children.
AB - This study was designed to assess whether the symptoms of posttraumatic stress
mediate or moderate the relationship between political stressors and emotional
and behavioral disorders in Palestinian children. It was hypothesized that (a)
posttraumatic stress and worry mediate the effect of political stressors on
behavioral and emotional disorders and (b) the relationship between political
stressors and behavioral and emotional disorders should be attenuated for
children with low levels of worry and posttraumatic stress and strengthened for
children with high levels of worry and posttraumatic stress. The total sample was
1267 school age children of both sexes with a mean age of 11.97 years. Interviews
were conducted with children at school. As hypothesized, the results indicated
that posttraumatic stress and worry mediated and moderated the relationship
between political stressors and emotional and behavioral disorders in children.
Cognitive-behavioral therapy may be used to reduce the incidence of posttraumatic
stress and decrease self-reported worry, somatic symptoms, general anxiety, and
depression among children exposed to political trauma. Cognitive-behavioral
treatment that exclusively targets excessive worry can lead to clinical change in
the other interacting subsystems at the cognitive, physiological, affective and
behavioral levels.
PMID- 22047000
TI - Different brain mechanisms between stereotype activation and application:
evidence from an ERP study.
AB - Stereotyping involves two processes in which first, social stereotypes are
activated (stereotype activation), and then, stereotypes are applied to given
targets (stereotype application). Previous behavioral studies have suggested that
these two processes are independent of each other and may have different
mechanisms. As few psychophysiological studies have given an integrated account
of these stages in stereotyping so far, this study utilized a trait
categorization task in which event-related potentials (ERPs) were used to explore
the brain mechanisms associated with the processes of stereotype activation and
its application. The behavioral (reaction time) and electrophysiological data
showed that stereotype activation and application were elicited respectively in
an affective valence identification subtask and in a semantic content judgment
subtask. The electrophysiological results indicated that the categorization
processes involved in stereotype activation to quickly identify stereotypic and
nonstereotypic information were quite different from those involved in the
application. During the process of stereotype activation, a P2 and N2 effect was
observed, indicating that stereotype activation might be facilitated by an early
attentional bias. Also, a late positive potential (LPP) was elicited, suggesting
that social expectancy violation might be involved. During the process of the
stereotype application, electrophysiological data showed a P2 and P3 effect,
indicating that stereotype application might be related to the rapid social
knowledge identification in semantic representation and thus may be associated
with an updating of existing stereotypic contents or a motivation to resolve the
inconsistent information. This research strongly suggested that different
mechanisms are involved in the stereotype activation and application processes.
PMID- 22047001
TI - Subjective wellbeing and its relationship with academic achievement and
multilinguality among Lebanese university students.
AB - The study investigated three subjective wellbeing (SWB) components, namely
positive affect (PA), negative affect (NA), and life satisfaction (LS), along
with optimism and self-esteem and their association with academic achievement and
multilinguality in a sample of 1401 Lebanese university students. As predicted,
optimism and self-esteem correlated positively with LS and PA, and negatively
with NA. Optimism, self-esteem and each of the SWB components jointly predicted
academic achievement (GPA), with PA being an individually significant positive
predictor. There were differences in the five key variables across language
groups, specifically between Arabic-only speakers and some other groups: Compared
Arabic-only speakers, bilingual speakers of Arabic and either English or French
scored higher on self-esteem, PA and optimism, and lower on NA, while trilingual
speakers of Arabic, English, and French scored higher on self-esteem, PA and LS.
Language grouping was a significant predictor of the SWB components, optimism,
and self-esteem even when controlling for GPA, socioeconomic status (SES), and
religion. Lastly, the relevance of SES and religion for the prediction of SWB is
discussed, and implications and future research questions are advanced.
PMID- 22047002
TI - Coverage of Russian psychological contributions in American psychology textbooks.
AB - Internationalizing psychology is an important component of current globalization
trends. American textbooks on the history of psychology and introductory
psychology were surveyed for the presence of historical and contemporary
important Russian psychologists to assess the current status of Russian-American
crossfertilization. Of a list of 97 important Russian psychologists, as
determined by the editors of the Russian journal Methodology and History in
Psychology, less than 22% are mentioned in the reviewed texts. The most common
names were Pavlov, Luria, and Vygotsky. As the internet is arguably the single
most important factor affecting the increase of international communication and
dissemination of knowledge, we also searched for these 97 names on various
websites, most notably Wikipedia and Google. Forty-one internet sites contained
some amount of biographical information about Russian psychologists. On
Wikipedia, 14 Russian psychologists had articles documenting biographical
information. We also developed a rubric to determine the amount of information
available on the internet for these psychologists and compared Wikipedia's mean
score with various other websites. Wikipedia pages on average had a significantly
higher score than the rest of the internet. Recommendations to improve Russian
coverage in America are provided and include: (1) developing pages on Wikipedia
and other virtual venues highlighting Russian contributions, (2) soliciting
articles for US journals from Russian psychologists, and (3) incorporating
Russian contributions in introductory and historical textbooks. We provide a
partial bibliography of Russian contributions that can be used by authors of such
textbooks. We would like to thank Dr Viktor Fedorovich Petrenko and Dr Igor
Nikolaevich Karitsky from the journal Methodology and History of Psychology for
supplying the names of the Russian psychologists. We would also like to express
our appreciation to Robert Garcia for reviewing and editing an earlier version of
this manuscript.
PMID- 22047003
TI - Insulin analogues: how observational studies provide key insights into management
of patients with type 2 diabetes mellitus.
AB - OBJECTIVE: The aim of this commentary was to evaluate the current evidence
regarding the use of synthetic insulin analogues in the 'real-world' clinic
setting for the treatment of type 2 diabetes mellitus (T2DM). METHODS: Relevant
publications were searched on PubMed MEDLINE, EMBASE, Cochrane Register of
Controlled Trials Google Scholar, NLM Gateway, Science Direct, Web of Science and
OVID for the period of January 2007 to June 2010. Articles were included if they
(a) provided specific study results on the use of insulin analogues in T2DM and
(b) gave sufficiently clear methodology details to establish treatment
strategies, diagnosis and diagnostic criteria using an observational study (OS)
design. RESULTS: Twenty one articles specifically addressing both type 2 diabetes
management and the use of synthetic insulin analogues were identified. Results
from recently published OS in patients with T2DM have shown, in the patient
populations tested, the effective initiation, optimization and switch to use of
insulin analogues in routine clinical settings (day-to-day common practice), with
a good safety profile. CONCLUSIONS: OS can provide clinicians with additional
insights into the management of T2DM patients in their practices. However, the
selection and initiation of insulin analogue regimens should be tailored to the
individual patient and be one that the physician is comfortable using.
PMID- 22047004
TI - Sponge-to-lamellar transition in a double-tail cationic surfactant/protic ionic
liquid system: structural and rheological analysis.
AB - The self-assembly of didodecyldimethylammonium bromide (DDAB) in a protic ionic
liquid, ethylammonium nitrate (EAN), in the high surfactant concentration regime
is studied using five different experimental techniques. A thermoreversible first
order sponge (L(3)) to lamellar (L(alpha)) transition occurring at [DDAB] > 80 wt
% was identified by (1) a sharp increase in the elastic and viscous moduli, (2) a
transition peak recorded by differential scanning calorimetry, (3) formation of
Maltese cross birefringence textures observed via polarizing optical microscopy,
(4) a decrease in the interbilayer mean distance measured by small angle neutron
scattering, and (5) an abrupt increase in the conductivity obstruction factor. In
contrast to aqueous DDAB solutions, this surfactant forms a stable L(3) phase in
EAN in a wide window of compositions and temperatures, which is potentially
useful for the synthesis of nanoporous materials. To the best of our knowledge,
this is the first evidence of the formation of the L(3) phase in an ionic liquid.
PMID- 22047006
TI - Road traffic crashes managed by Rescue 1122 in Lahore, Pakistan.
AB - The objective of this retrospective study was to describe demographic
characteristics, injury patterns and causes of road traffic crashes (RTCs)
managed by Rescue 1122 in Lahore, Pakistan during the period 2005-2010. In total
123,268 RTCs were reported and responded by Rescue 1122 ambulance service during
the study period. Of the 132,504 victims of RTCs, there were 67% male and 33%
female subjects, and the maximum share (65%) was reported among people aged 16-35
years. Motorcyclists were involved in 45% of crashes, with over-speeding (40%)
found to be the major reason of these collisions. Similarly, minor injuries (65%)
and fractures (25%) were the most reported outcome of these crashes. It is
concluded that data from ambulance services, if appropriately collected, can
provide valuable epidemiological information to monitor RTCs in developing
countries. However, in Pakistan, the collection of data as well as the
registration process needs further improvement.
PMID- 22047007
TI - Prevention and management of transplant-associated diabetes.
AB - INTRODUCTION: New-onset diabetes after transplantation (NODAT) is considered to
be a major cause of cardiovascular disease and death among patients with a
functioning allograft. A major challenge is to reduce the incidence of NODAT and
to treat it optimally once it has occurred. AREAS COVERED: This review presents
current data on how to prevent NODAT in patients at risk, with a focus on
modifications in the immunosuppressive regimen. Current suggestions for detection
and treatment of NODAT are also presented. EXPERT OPINION: Prevention of NODAT is
possible by assessing the patient's glycemic risk prior to transplantation and
tailoring the treatment (e.g., choice and dosage of immunosuppressive agents)
after transplantation. An oral glucose tolerance test is still the gold standard
to detect NODAT in patients at risk (prediabetes) but algorithms can be used to
select those who should be tested. The treatment of NODAT involves a broad
approach on risk factors for cardiovascular events and graft loss. Future studies
on the use of oral hypoglycemic agents in NODAT are still needed.
PMID- 22047005
TI - Vitamin D - roles in women's reproductive health?
AB - In the past few years a growing interest in vitamin D can be observed in the lay
and biomedical literature due to findings demonstrating a low vitamin D status in
the population. In addition to its importance for the regulation of calcium and
phosphorus homeostasis recent epidemiologic studies have observed relationships
between low vitamin D levels and multiple disease states. This secosteroid
hormone also regulates the expression of a large number of genes in reproductive
tissues implicating a role for vitamin D in female reproduction. In this report
we summarize the recent evidence that vitamin D status influences female
reproductive and pregnancy outcomes. Human and animal data suggest that low
vitamin D status is associated with impaired fertility, endometriosis and
polycystic ovary syndrome. Evidence from observational studies shows higher rates
of preeclampsia, preterm birth, bacterial vaginosis and gestational diabetes in
women with low vitamin D levels. However, confirmation of experimental
observations establishing an association of vitamin D deficiency with adverse
reproductive outcomes by high quality observational and large-scale randomized
clinical trials is still lacking. The determination of optimal 25(OH)D3 levels in
the reproductive period and the amount of vitamin D supplementation required to
achieve those levels for the numerous actions of vitamin D throughout a woman's
life would have important public health implications.
PMID- 22047008
TI - Density functional theory study of the oxidation of ammonia on the IrO2(110)
surface.
AB - In this study, we employed density functional theory (DFT) to investigate the
oxidation of ammonia (NH(3)) on the IrO(2)(110) surface. We characterized the
possible reaction pathways for the dehydrogenation of NH(x) species (x = 1-3) and
for the formation of the oxidation products N(2), N(2)O, NO, NO(2), and H(2)O.
The presence of oxygen atoms on coordinatively unsaturated sites (O(cus)) of the
oxygen-rich IrO(2)(110) surface promotes the oxidation of NH(3) on the surface.
In contrast, NH(3) molecules prefer undergoing desorption over oxidation on the
stoichiometric IrO(2)(110) surface. Moreover, the O(cus) atoms are also the major
oxidants leading to the formation of oxidation products; none of the oxidations
mediated by the bridge oxygen atoms were favorable reactions. The energy barrier
for formation of H(2)O as a gaseous oxidation product on the IrO(2)(110) surface
is high (from 1.83 to 2.29 eV), potentially leading to the formation of nitrogen
atom-containing products at high temperature. In addition, the selectivity toward
the nitrogen-atom-containing products is dominated by the coverage of O(cus)
atoms on the surface; for example, a higher coverage of O(cus) atoms results in
greater production of nitrogen oxides (NO, NO(2)).
PMID- 22047009
TI - Grahamines A-E, cyclobutane-centered tropane alkaloids from the aerial parts of
Schizanthus grahamii.
AB - Schizanthus grahamii is an endemic Chilean plant that is known to contain tropane
alkaloids. Five new alkaloids, grahamines A-E (1-5), were isolated and
characterized by extensive spectroscopic analysis. Their structures were
determined to be 2-{[(3alpha-hydroxytropo-6beta-yl)oxy]carbonyl}-2-methyl-3
{[((6beta-angeloyloxy)-3alpha-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylic acid
(1), 2-{[(3alpha-hydroxytropo-6beta-yl)oxy]carbonyl}-2-methyl-3-{[((6beta
tigloyloxy)-3alpha-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylic acid (2), 1
methyl-2-{[(3alpha-hydroxytropo-6beta-yl)oxy]carbonyl}-4-{[((6beta-angeloyloxy)
3alpha-yl)oxy]carbonyl}-3-phenylcyclobutanecarboxylic acid (3), 1,2-bis{[(3alpha
hydroxytropo-6beta-yl)oxy]carbonyl}-2-methyl-3-{[((6beta-angeloyloxy)-3alpha
yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylate (4), and 1-{[(3alpha
mesaconyloxytropo-6beta-yl)oxy]carbonyl}-2-{[(3alpha-hydroxytropo-6beta
yl)oxy]carbonyl}-2-methyl-3-{[((6beta-angeloyloxy)-3alpha-yl)oxy]carbonyl}-4
phenylcyclobutanecarboxylate (5).
PMID- 22047010
TI - Fluorescence and visual detection of single nucleotide polymorphism using
cationic conjugated polyelectrolyte.
AB - We report a simple assay for visual detection of single nucleotide polymorphisms
(SNPs) with good sensitivity and selectivity. The selectivity is determined by
Escherichia coli (E. coli) DNA ligase mediated circular formation upon
recognition of the point mutation on DNA targets. Rolling cycle amplification
(RCA) of the perfect-matched DNA target is then initiated using the in situ
formed circular template in the presence of Phi29 enzyme. Due to amplification of
the DNA target, the RCA product has a tandem-repeated sequence, which is
significantly longer than that for the SNP strand. Direct addition of a cationic
conjugated polymer of poly[9,9'-bis(6'-(N,N,N-trimethylammonium)hexyl)fluorene-co
9,9'-bis(2-(2-(2-(N,N,N-trimethylammonium)ethoxyl)-ethoxy)-ethyl)fluorene
tetrabromide] containing 20 mol% 2,1,3-benzothiadiazole (PFBT(20)) into the RCA
solution leads to blue-whitish fluorescent color for SNP strand and yellowish
fluorescent color for amplified DNA, due to PFBT(20)/DNA complexation induced
intrachain/interchain energy transfer. To further improve the contrast for visual
detection, FAM-labeled peptide nucleic acid (PNA) was hybridized to each
amplified sequence, which is followed by the addition of poly{2,7-[9,9-bis(6'
N,N,N-trimethylammoniumhexyl)]fluorene-co-2,5-difluoro-1,4-phenylene dibromide}
(PFP). The PNA/DNA hybridization brings PFP and FAM-PNA into close proximity for
energy transfer, and the solution fluorescent color appears green in the presence
of target DNA with a detection limit of 1 nM, which is significantly improved as
compared to that for most reported visual SNP assay.
PMID- 22047011
TI - Carbon aerogel composites prepared by ambient drying and using oxidized
polyacrylonitrile fibers as reinforcements.
AB - Carbon fiber-reinforced carbon aerogel composites (C/CAs) for thermal insulators
were prepared by copyrolysis of resorcinol-formaldehyde (RF) aerogels reinforced
by oxidized polyacrylonitrile (PAN) fiber felts. The RF aerogel composites were
obtained by impregnating PAN fiber felts with RF sols, then aging, ethanol
exchanging, and drying at ambient pressure. Upon carbonization, the PAN fibers
shrink with the RF aerogels, thus reducing the difference of shrinkage rates
between the fiber reinforcements and the aerogel matrices, and resulting in C/CAs
without any obvious cracks. The three point bend strength of the C/CAs is 7.1 +/-
1.7 MPa, and the thermal conductivity is 0.328 W m(-1) K(-1) at 300 degrees C in
air. These composites can be used as high-temperature thermal insulators (in
inert atmospheres or vacuum) or supports for phase change materials in thermal
protection system.
PMID- 22047012
TI - Folding-promoted TBACl-mediated chemo- and regioselective demethylations of
methoxybenzene-based macrocyclic pentamers.
AB - Tetrabutylammonium chloride (TBACl) salt alone has not been shown previously to
be capable of removing methoxy groups. It is demonstrated here that the use of
TBACl achieves efficient folding-promoted chemo- and regioselective
demethylations, eliminating up to two out of five methyl groups situated in
similar macrocyclic chemical microenvironments.
PMID- 22047013
TI - A technical modification for percutaneous tracheostomy: prospective case series
study on one hundred patients.
AB - The purpose of this study is to describe a technical modification of
percutaneous tracheostomy that combines principles of the Percu TwistTM and the
Griggs-Portex(r) methods in a reusable kit. One hundred patients underwent the
procedure. There were no false passage, tube misplacement, or deaths related to
the procedure. There were two minor bleedings managed conservatively. The
technical modification described in this study is safe and simple to execute.
PMID- 22047014
TI - Fast MCMC sampling for hidden Markov Models to determine copy number variations.
AB - BACKGROUND: Hidden Markov Models (HMM) are often used for analyzing Comparative
Genomic Hybridization (CGH) data to identify chromosomal aberrations or copy
number variations by segmenting observation sequences. For efficiency reasons the
parameters of a HMM are often estimated with maximum likelihood and a
segmentation is obtained with the Viterbi algorithm. This introduces considerable
uncertainty in the segmentation, which can be avoided with Bayesian approaches
integrating out parameters using Markov Chain Monte Carlo (MCMC) sampling. While
the advantages of Bayesian approaches have been clearly demonstrated, the
likelihood based approaches are still preferred in practice for their lower
running times; datasets coming from high-density arrays and next generation
sequencing amplify these problems. RESULTS: We propose an approximate sampling
technique, inspired by compression of discrete sequences in HMM computations and
by kd-trees to leverage spatial relations between data points in typical data
sets, to speed up the MCMC sampling. CONCLUSIONS: We test our approximate
sampling method on simulated and biological ArrayCGH datasets and high-density
SNP arrays, and demonstrate a speed-up of 10 to 60 respectively 90 while
achieving competitive results with the state-of-the art Bayesian approaches.
AVAILABILITY: An implementation of our method will be made available as part of
the open source GHMM library from http://ghmm.org.
PMID- 22047015
TI - Feasibility and willingness-to-pay for integrated community-based tuberculosis
testing.
AB - BACKGROUND: Community-based screening for TB, combined with HIV and syphilis
testing, faces a number of barriers. One significant barrier is the value that
target communities place on such screening. METHODS: Integrated testing for TB,
HIV, and syphilis was performed in neighborhoods identified using geographic
information systems-based disease mapping. TB testing included skin testing and
interferon gamma release assays. Subjects completed a survey describing disease
risk factors, healthcare access, healthcare utilization, and willingness to pay
for integrated testing. RESULTS: Behavioral and social risk factors among the 113
subjects were prevalent (71% prior incarceration, 27% prior or current crack
cocaine use, 35% homelessness), and only 38% had a regular healthcare provider.
The initial 24 subjects reported that they would be willing to pay a median $20
(IQR: 0-100) for HIV testing and $10 (IQR: 0-100) for TB testing when the
question was asked in an open-ended fashion, but when the question was changed to
a multiple-choice format, the next 89 subjects reported that they would pay a
median $5 for testing, and 23% reported that they would either not pay anything
to get tested or would need to be paid $5 to get tested for TB, HIV, or syphilis.
Among persons who received tuberculin skin testing, only 14/78 (18%) participants
returned to have their skin tests read. Only 14/109 (13%) persons who underwent
HIV testing returned to receive their HIV results. CONCLUSION: The relatively
high-risk persons screened in this community outreach study placed low value on
testing. Reported willingness to pay for such testing, while low, likely
overestimated the true willingness to pay. Successful TB, HIV, and syphilis
integrated testing programs in high risk populations will likely require one
visit diagnostic testing and incentives.
PMID- 22047016
TI - TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver
cells.
AB - Titanium dioxide nanoparticles (TiO(2) NPs), widely used in consumer products,
paints, pharmaceutical preparations and so on, have been shown to induce
cytotoxicity, genotoxicity and carcinogenic responses in vitro and in vivo. The
present study revealed that TiO(2) NPs induce significant (p < 0.05) oxidative
DNA damage by the Fpg-Comet assay even at 1 ug/ml concentration. A corresponding
increase in the micronucleus frequency was also observed. This could be
attributed to the reduced glutathione levels with concomitant increase in lipid
peroxidation and reactive oxygen species generation. Furthermore, immunoblot
analysis revealed an increased expression of p53, BAX, Cyto-c, Apaf-1, caspase-9
and caspase-3 and decreased the level of Bcl-2 thereby indicating that apoptosis
induced by TiO(2) NPs occurs via the caspase-dependent pathway. This study
systematically shows that TiO(2) NPs induce DNA damage and cause apoptosis in
HepG2 cells even at very low concentrations. Hence the use of such nanoparticles
should be carefully monitored.
PMID- 22047017
TI - The kinetics of cell surface receptor expression in children perinatally exposed
to polychlorinated biphenyls.
AB - Exposure to polychlorinated biphenyls (PCBs) during pre-natal and early life can
alter normal immune system development. Blood specimens from newborns, 6-, and 16
month-old infants were collected in the Michalovce and Svidnik/Stropkov
districts, areas with, respectively, high and low environmental PCB
contamination, and lymphocyte receptor expression was evaluated by multi-color
flow cytometry. The results indicate that the percentage of lymphoid dendritic
cells (DC) and naive/resting T-lymphocytes were significantly increased at 6
months in Michalovce as compared to the same cell types in cord blood samples (p
< 0.001), whereas natural regulatory T-lymphocytes and suppressor inducer T
lymphocytes were reduced (p < 0.001). Overall, a positive linear correlation of
terminally differentiated effector memory (TEM) T-lymphocyte population with age,
but a negative linear correlation for myeloid DC from birth to 6-months in both
regions were found. Michalovce samples indicated significantly higher expression
of memory T-lymphocytes (birth, 6(th), and 16(th) month), TEM T-lymphocytes
(birth and 6(th) month), and lymphoid DC (6(th) month) compared to the
Svidnik/Stropkov regions. After adjustment for relevant covariates, such as
maternal age, parity, season of birth, breastfeeding, birth weight, and gender,
the myeloid DC, suppressor inducer T-lymphocytes, truly naive helper/inducer T
lymphocytes, and TEM T-lymphocytes remained significantly different between
districts in cord blood samples. The multivariate analysis models for 6- and 16
month samples showed district differences in all cellular determinants, except
for lymphoid DC and macrophage-like cells. This study provides the first evidence
that pre-natal and early post-natal exposure to PCBs affects the dynamics of cell
surface receptor expression on lymphoid DC and DC-like cells, suggesting impaired
immunologic development following pre-natal and early post-natal PCB exposure.
PMID- 22047018
TI - Statement of retraction.
PMID- 22047019
TI - Course and prognosis of recovery for chronic non-specific low back pain: design,
therapy program and baseline data of a prospective cohort study.
AB - BACKGROUND: There has been increasing focus on factors predicting the development
of chronic musculoskeletal disorders. For patients already experiencing chronic
non-specific low back pain it is also relevant to investigate which prognostic
factors predict recovery. We present the design of a cohort study that aims to
determine the course and prognostic factors for recovery in patients with chronic
non-specific low back pain. METHODS/DESIGN: All participating patients were
recruited (Jan 2003-Dec 2008) from the same rehabilitation centre and were
evaluated by means of (postal) questionnaires and physical examinations at
baseline, during the 2-month therapy program, and at 5 and 12 months after start
of therapy. The therapy protocol at the rehabilitation centre used a bio
psychosocial approach to stimulate patients to adopt adequate (movement)
behaviour aimed at physical and functional recovery. The program is part of
regular care and consists of 16 sessions of 3 hours each, over an 8-week period
(in total 48 hours), followed by a 3-month self-management program. The primary
outcomes are low back pain intensity, disability, quality of life, patient's
global perceived effect of recovery, and participation in work. Baseline
characteristics include information on socio-demographics, low back pain,
employment status, and additional clinical items status such as fatigue, duration
of activities, and fear of kinesiophobia. Prognostic variables are determined for
recovery at short-term (5 months) and long-term (12 months) follow-up after start
of therapy. DISCUSSION: In a routine clinical setting it is important to provide
patients suffering from chronic non-specific low back pain with adequate
information about the prognosis of their complaint.
PMID- 22047020
TI - Assessing diversity of the female urine microbiota by high throughput sequencing
of 16S rDNA amplicons.
AB - BACKGROUND: Urine within the urinary tract is commonly regarded as "sterile" in
cultivation terms. Here, we present a comprehensive in-depth study of bacterial
16S rDNA sequences associated with urine from healthy females by means of culture
independent high-throughput sequencing techniques. RESULTS: Sequencing of the
V1V2 and V6 regions of the 16S ribosomal RNA gene using the 454 GS FLX system was
performed to characterize the possible bacterial composition in 8 culture
negative (<100,000 CFU/ml) healthy female urine specimens. Sequences were
compared to 16S rRNA databases and showed significant diversity, with the
predominant genera detected being Lactobacillus, Prevotella and Gardnerella. The
bacterial profiles in the female urine samples studied were complex; considerable
variation between individuals was observed and a common microbial signature was
not evident. Notably, a significant amount of sequences belonging to bacteria
with a known pathogenic potential was observed. The number of operational
taxonomic units (OTUs) for individual samples varied substantially and was in the
range of 20-500. CONCLUSIONS: Normal female urine displays a noticeable and
variable bacterial 16S rDNA sequence richness, which includes fastidious and
anaerobic bacteria previously shown to be associated with female urogenital
pathology.
PMID- 22047022
TI - Ruthenium-catalyzed meta sulfonation of 2-phenylpyridines.
AB - A selective catalytic meta sulfonation of 2-phenylpyridines was found to occur in
the presence of (arene)ruthenium(II) complexes upon reaction with sulfonyl
chlorides. The 2-pyridyl group facilitates the formation of a stable Ru-C(aryl)
sigma bond that induces a strong para-directing effect. Electrophilic aromatic
substitution proceeds with the sulfonyl chloride to furnish a sulfone at the
position meta to the chelating group. This new catalytic process offers access to
atypical regioselectivity for reactions involving chelation-assisted
cyclometalation.
PMID- 22047023
TI - Impact of an individualist vs. collectivist context on the social valorization of
internal explanations.
AB - The theory of the norm of internality emphasizes the role of Western
individualism in the normativity of internal explanations. The present study
examines the link between the social value accorded to targets expressing
internal vs. external explanations and individualist vs. collectivist contexts.
Sixty-three male and female French management sciences students evaluated two
targets (internal vs. external) in a simulated recruitment situation. The job
vacancy was partially manipulated to create individualist vs. collectivist
contexts. Participants were asked to state whether or not they would recruit the
targets and to describe the targets on traits relating to social utility (market
value) and social desirability (likeability). As expected, the results showed
that the effect of the targets' internality on recruitment judgments and
perceived social utility was stronger in the individualist context than in the
collectivist context. However, the analysis also revealed that the participant's
gender moderated the impact of the context on the evaluation of the targets. The
results showed that the context strongly affected the men's judgments, whereas it
had no effect on the women's judgments.
PMID- 22047021
TI - Translesion DNA synthesis in the context of cancer research.
AB - During cell division, replication of the genomic DNA is performed by high
fidelity DNA polymerases but these error-free enzymes can not synthesize across
damaged DNA. Specialized DNA polymerases, so called DNA translesion synthesis
polymerases (TLS polymerases), can replicate damaged DNA thereby avoiding
replication fork breakdown and subsequent chromosomal instability.We focus on the
involvement of mammalian TLS polymerases in DNA damage tolerance mechanisms. In
detail, we review the discovery of TLS polymerases and describe the molecular
features of all the mammalian TLS polymerases identified so far. We give a short
overview of the mechanisms that regulate the selectivity and activity of TLS
polymerases. In addition, we summarize the current knowledge how different types
of DNA damage, relevant either for the induction or treatment of cancer, are
bypassed by TLS polymerases. Finally, we elucidate the relevance of TLS
polymerases in the context of cancer therapy.
PMID- 22047024
TI - Barriers to physical activity in older adults in Germany: a cross-sectional
study.
AB - BACKGROUND: Data on barriers to physical activity in older adults in Germany are
scarce. The aim of this study was to analyse barriers to physical activity in a
cohort of older adults, allowing comparisons between men and women, and age
groups. METHODS: 1,937 older adults with a median age of 77 (range 72-93) years
(53.3% female) took part in the 7-year follow-up telephone interviews of the
getABI cohort. Participants who stated that they did not get enough physical
activity were surveyed with respect to barriers to physical activity. Barriers
were analysed for all respondents, as well as by sex and age group for cases with
complete data. Multivariate logistic regression analysis was performed to
evaluate differences between sexes and age groups. The level of significance
(alpha < 0.05) was adjusted for multiple testing according to Bonferroni (p <
.004). RESULTS: 1,607 (83.0%) participants stated that they were sufficiently
physically active. 286 participants rated their physical activity as insufficient
and responded to questions on barriers to physical activity completely. The three
most frequently cited barriers were poor health (57.7%), lack of company (43.0%),
and lack of interest (36.7%). Lack of opportunities for sports or leisure
activities (30.3% vs. 15.6%), and lack of transport (29.0% vs. 7.1%) were more
frequently stated by female respondents than male respondents. These differences
between men and women were significant (p = .003; p < .001) after adjustment for
respondents' age. Analyses by age groups revealed that poor health was more
frequently considered a barrier to physical activity by participants aged 80+
years compared to the younger age group (71.1% vs. 51.5%). This age-dependent
difference was significant (p = .002) irrespective of the participants' sex.
CONCLUSIONS: The present study provides relevant data on barriers to physical
activity in older adults. By revealing appreciable differences between men and
women, and age groups, this study has implications for efforts to increase older
adults' physical activity. Promotion and intervention strategies should consider
the barriers and tailor measures to the specific needs of older adults in order
to reduce their constraints to physical activity.
PMID- 22047025
TI - Enantiomer resolution by pressure increase: inferences from experimental and
topological results for the binary enantiomer system (R)- and (S)-mandelic acid.
AB - In pharmacy, racemic compounds are often problematic, because generally only one
of the enantiomers possesses therapeutic activity and it is often difficult to
separate them. Even though this problem is likely as old as the pharmaceutical
industry, one thermodynamically obvious way of separating racemic crystals has
never been studied experimentally, which is by using pressure. Data have been
obtained on the equilibria of the (R)- and (S)-mandelic acid system as a function
of pressure and temperature. With the use of thermodynamic arguments including
the Clapeyron, Schroder, and Prigogine-Defay equations, it has been demonstrated
that the conglomerate (crystals of separated enantiomers) becomes more stable
than the racemic compound at approximately 0.64 GPa and 460 K. Even though this
pressure is still higher than at the bottom of the Mariana Trench, there are no
technical obstacles to produce such conditions, making pressure a viable option
for separating enantiomers.
PMID- 22047028
TI - Development of a multilevel approach for the evaluation of nanomaterials'
toxicity.
AB - AIM: To develop a multilevel approach that includes different toxicity tests and
gene-expression studies for toxicity evaluation of engineered nanomaterials
developed for biomedical applications. MATERIALS & METHODS: K-562, MCF-7 and U
937 human-derived cell lines were used as models for in vitro toxicity tests.
These tests included viability assays (3-[4,5-dimethylthiazol-2-yl]-5-[3
carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium [MTS] assay); evaluation
of apoptosis/necrosis by propidium iodide staining and DNA laddering assay;
evaluation of mitochondrial toxicity (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl
benzimidazolcarbocyanine iodide [JC-1] assay); transmission electron microscopy
analysis and gene expression analysis by DNA microarray. For in vivo toxicity
evaluation, Swiss mice were used for monitoring acute or chronic effects. Two
superparamagnetic contrast agents approved for human use (Resovist and Primovist)
and two new lanthanide-based luminescent nanoparticles were tested. RESULTS &
DISCUSSION: The nanomaterials approved for human use did not show significant
toxicities in our assays. Toxicity studies performed on lanthanide-based
nanoparticles (EDTA120 and EDTA120D) complexed with the chelating agent EDTA
revealed that these nanomaterials induced necrosis in U-937 and K-562 cells while
no toxicity was observed in MCF-7 cells. Moreover, no in vivo effects have been
observed. The comparative analysis of the nanomaterials and their separated
components showed that the toxicity in U-937 and K-562 cells was mainly due to
the presence of EDTA. CONCLUSION: The multilevel approach proved to be useful for
nanomaterial toxicity characterization. In particular, for the lanthanide-based
nanoparticles tested in this work, the EDTA was identified as the main cause of
the toxicity in vitro, suggesting a possible applicability of these nanoparticle
suspensions for in vivo optical imaging.
PMID- 22047027
TI - Cancer control and prevention by nutrition and epigenetic approaches.
AB - SIGNIFICANCE: Epigenetics involves alterations in gene expression without
changing the nucleotide sequence. Because some epigenetic changes can be reversed
chemically, epigenetics has tremendous implications for disease intervention and
treatment. RECENT ADVANCES: After epigenetic components in cancer were
characterized, genes and pathways are being characterized in other diseases such
as diabetes, obesity, and neurological disorders. Observational, experimental,
and clinical studies in different diseases have shown that nutrients influence
epigenetic regulation. Nutrients such as folic acid that supply methyl groups
have been shown to have a protective effect in colon cancer. CRITICAL ISSUES:
Identifying steps during epigenetic regulation and developing intervention and
treatment agents are the critical issues in the field. FUTURE DIRECTIONS:
Following completion and validation of key observational studies in nutritional
epigenetics, strategies can be developed for cancer control and treatment.
PMID- 22047030
TI - Editorial.
PMID- 22047029
TI - Mechanism of titania deposition into cylindrical poly(styrene-block-4 vinyl
pyridine) block copolymer templates.
AB - A simple and effective way for TiO(2) to be deposited on silicon or indium tin
oxide (ITO) substrates has been achieved by using a poly(styrene-block-4-vinyl
pyridine) (PS-b-P4VP) block copolymer template. In particular, a mechanism for
the formation of TiO(2) within the P4VP phase was developed. Within this model,
the TiO(2) deposition occurs by swelling of the protonated P4VP segments followed
by transport of Ti precursor, probably protonated Ti(OH)(4) given the low pH
conditions used, into the swollen P4VP followed by condensation into TiO(2)
during the heating/plasma etch processes. TiO(2) nanostructure morphology is
affected by pH and deposition temperatures, because these parameters affect the
degree of protonation of P4VP segments and diffusion of the titanium(IV)
bis(ammonium lactato)dihydroxide (TALH) precursor into the film. A pH range of
2.1-2.5 for silicon substrates and pH = 2.1 for ITO substrates gave the narrower
TiO(2) nanostructures distributions, and deposition at 70 degrees C gave TiO(2)
nanostructures with more regular arrangements and smoother surface than those
deposited at room temperature. The use of 1,4-diiodobutane as a P4VP cross
linking compound is demonstrated to be a critical parameter for maintaining good
cylindrical surface morphology for both the block copolymer template and the
TiO(2) nanostructures.
PMID- 22047031
TI - Miscellaneous.
PMID- 22047032
TI - Erratum.
PMID- 22047035
TI - A step beyond the Feltham-Enemark notation: spectroscopic and correlated ab
initio computational support for an antiferromagnetically coupled M(II)-(NO)-
description of Tp*M(NO) (M = Co, Ni).
AB - Multiple spectroscopic and computational methods were used to characterize the
ground-state electronic structure of the novel {CoNO}(9) species Tp*Co(NO) (Tp* =
hydro-tris(3,5-Me(2)-pyrazolyl)borate). The metric parameters about the metal
center and the pre-edge region of the Co K-edge X-ray absorption spectrum were
reproduced by density functional theory (DFT), providing a qualitative
description of the Co-NO bonding interaction as a Co(II) (S(Co) = 3/2) metal
center, antiferromagnetically coupled to a triplet NO(-) anion (S(NO) = 1), an
interpretation of the electronic structure that was validated by ab initio
multireference methods (CASSCF/MRCI). Electron paramagnetic resonance (EPR)
spectroscopy revealed significant g-anisotropy in the S = 1/2 ground state, but
the linear-response DFT performed poorly at calculating the g-values. Instead,
CASSCF/MRCI computational studies in conjunction with quasi-degenerate
perturbation theory with respect to spin-orbit coupling were required for
obtaining accurate modeling of the molecular g-tensor. The computational portion
of this work was extended to the diamagnetic Ni analogue of the Co complex,
Tp*Ni(NO), which was found to consist of a Ni(II) (S(Ni) = 1) metal center
antiferromagnetically coupled to an S(NO) = 1 NO(-). The similarity between the
Co and Ni complexes contrasts with the previously studied Cu analogues, for which
a Cu(I) bound to NO(0) formulation has been described. This discrepancy will be
discussed along with a comparison of the DFT and ab initio computational methods
for their ability to predict various spectroscopic and molecular features.
PMID- 22047036
TI - Rapid deposition of transparent super-hydrophobic layers on various surfaces
using microwave plasma.
AB - We report herein on a very fast and simple process for the fabrication of
transparent superhydrophobic surfaces by using microwave (MW) plasma. It was
found that the reaction of various organic liquids in MW argon plasma yields
hydrophobic polymeric layers on a large assortment of surfaces, including glass,
polymeric surfaces, ceramics, metals, and even paper. In most cases, these
polymers are deposited as a rough layer composed of 10-15 nm nanoparticles (NPs).
This roughness, together with the chemical hydrophobic nature of the coated
materials, is responsible for the superhydrophobic nature of the surface. The
typical reaction time of the coating procedure was 1-10 s. The stability of these
superhydrophobic surfaces was examined outdoors, and was found to last 2-5 days
under direct exposure to the environment and to last 2 months when the sample was
protected by a quartz cover. A detailed characterization study of the chemical
composition of the layers followed using XPS, solid-state NMR, and IR
measurements. Modifications were introduced in the products leading to a
substantial improvement in the stability of the products outdoors.
PMID- 22047037
TI - A powerful palladium-catalyzed multicomponent process for the preparation of
oxazolines and benzoxazoles.
AB - Efficient and convenient three-component couplings of an aryl halide, isocyanide,
and an amino alcohol under palladium catalysis provide a range of oxazolines and
benzoxazoles in excellent yield.
PMID- 22047038
TI - Intra aortic balloon pump: literature review of risk factors related to
complications of the intraaortic balloon pump.
AB - The increasing use of the intra aortic balloon pump is attributed to the
relatively easy percutaneous insertion and the low threshold of use over the past
few years, especially in elderly patients with multi-vessel diseases and an
affected ejection fraction.Unfortunately, the clinical assessment of the
complications associated to the use of this supporting device, underestimates the
frequency of such complications.This report has looked at the current literature
and attempt to identify incremental risk factors related to the development of
adverse effects during support with an intaaortic balloon pump.The paper
concludes that in contrary to early reports, newer studies have shown that
complications following intraaortic balloon pump treatment, is decreasing.
Moreover the literature suggests that the thrombosis and infective complications
are relevant to the duration of the pump treatment, while the ischemic problems
of the limbs are mostly linked to the atherosclerotic status of the common
femoral artery.
PMID- 22047039
TI - Evolutionary history of barley cultivation in Europe revealed by genetic analysis
of extant landraces.
AB - BACKGROUND: Understanding the evolution of cultivated barley is important for two
reasons. First, the evolutionary relationships between different landraces might
provide information on the spread and subsequent development of barley
cultivation, including the adaptation of the crop to new environments and its
response to human selection. Second, evolutionary information would enable
landraces with similar traits but different genetic backgrounds to be identified,
providing alternative strategies for the introduction of these traits into modern
germplasm. RESULTS: The evolutionary relationships between 651 barley landraces
were inferred from the genotypes for 24 microsatellites. The landraces could be
divided into nine populations, each with a different geographical distribution.
Comparisons with ear row number, caryopsis structure, seasonal growth habit and
flowering time revealed a degree of association between population structure and
phenotype, and analysis of climate variables indicated that the landraces are
adapted, at least to some extent, to their environment. Human selection and/or
environmental adaptation may therefore have played a role in the origin and/or
maintenance of one or more of the barley landrace populations. There was also
evidence that at least some of the population structure derived from geographical
partitioning set up during the initial spread of barley cultivation into Europe,
or reflected the later introduction of novel varieties. In particular, three
closely-related populations were made up almost entirely of plants with the
daylength nonresponsive version of the photoperiod response gene PPD-H1,
conferring adaptation to the long annual growth season of northern Europe. These
three populations probably originated in the eastern Fertile Crescent and entered
Europe after the initial spread of agriculture. CONCLUSIONS: The discovery of
population structure, combined with knowledge of associated phenotypes and
environmental adaptations, enables a rational approach to identification of
landraces that might be used as sources of germplasm for breeding programs. The
population structure also enables hypotheses concerning the prehistoric spread
and development of agriculture to be addressed.
PMID- 22047040
TI - Structures, energies, bonding, and NMR properties of pnicogen complexes H2XP:NXH2
(X ? H, CH3, NH2, OH, F, Cl).
AB - Ab initio calculations have been carried out in a systematic investigation of
P...N pnicogen complexes H(2)XP:NXH(2) for X ? H, CH(3), NH(2), OH, F, and Cl, as
well as selected complexes with different substituents X bonded to P and N.
Binding energies for complexes H(2)XP:NXH(2) range from 8 to 27 kJ mol(-1) and
increase to 39 kJ mol(-1) for H(2)FP:N(CH(3))H(2). Equilibrium structures have a
nearly linear A-P-N arrangement, with A being the atom directly bonded to P.
Binding energies correlate with intermolecular N-P distances as well as with
bonding parameters obtained from AIM and SAPT analyses. Complexation increases
(31)P chemical shieldings in complexes with binding energies greater than 19 kJ
mol(-1). One-bond spin-spin coupling constants (1p)J(N-P) across the pnicogen
interaction exhibit a quadratic dependence on the N-P distance for complexes
H(2)XP:NXH(2), similar to the dependence of (2h)J(X-Y) on the X-Y distance for
complexes with X-H...Y hydrogen bonds. However, when the mixed complexes
H(2)XP:NX'H(2) are included, the curvature of the trendline changes and the good
correlation between (1p)J(N-P) and the N-P distance is lost.
PMID- 22047041
TI - Biofilm and planktonic pneumococci demonstrate disparate immunoreactivity to
human convalescent sera.
AB - BACKGROUND: Streptococcus pneumoniae (the pneumococcus) is the leading cause of
otitis media, community-acquired pneumonia (CAP), sepsis, and meningitis. It is
now evident that S. pneumoniae forms biofilms during nasopharyngeal colonization;
the former which facilitates persistence, the latter, a prerequisite for
subsequent development of invasive disease. Proteomic evaluation of S. pneumoniae
suggests the antigen profile available for host-recognition is altered as a
consequence of biofilm growth. This has potentially meaningful implications in
regards to adaptive immunity and protection from disseminated disease. We
therefore examined the antigen profile of biofilm and planktonic pneumococcal
cell lysates, tested their reactivity with human convalescent sera and that
generated against biofilm pneumococci, and examined whether immunization with
biofilm pneumococci protected mice against infectious challenge. RESULTS: Biofilm
pneumococci have dramatically altered protein profiles versus their planktonic
counterparts. During invasive disease the humoral immune response is skewed
towards the planktonic protein profile. Immunization with biofilm bacteria does
not elicit a strong-cross-reactive humoral response against planktonic bacteria
nor confer resistance against challenge with a virulent isolate from another
serotype. We identified numerous proteins, including Pneumococcal serine-rich
repeat protein (PsrP), which may serve as a protective antigens against both
colonization and invasive disease. CONCLUSION: Differential protein production by
planktonic and biofilm pneumococci provides a potential explanation for why
individuals remain susceptible to invasive disease despite previous colonization
events. These findings also strongly suggest that differential protein production
during colonization and disease be considered during the selection of antigens
for any future protein vaccine.
PMID- 22047042
TI - Porphyromonas gingivalis accelerates atherosclerosis in C57BL/6 mice fed a high
fat diet.
AB - OBJECTIVE: Porphyromonas gingivalis has been shown to accelerate atherosclerotic
lesion development in atherosclerotic apo E-deficient mice. Here, we investigated
whether repeated P. gingivalis injection affected the inflammatory and
atherosclerotic responses of C57BL/6 mice fed a high-fat diet (HFD). MATERIALS
AND METHODS: Eight-week-old C57BL/6 mice fed either HFD or a regular chow diet
(RD) were inoculated intravenously with P. gingivalis or phosphate-buffered
saline three times per week for 10 weeks and sacrificed at 19 weeks of age.
Atheromatous lesions in the proximal aorta of each animal were analyzed
histomorphometrically, and the serum cytokine and C-reactive protein (CRP) levels
were determined. RESULTS: Long-term HFD feeding as compared to RD feeding led to
a slight increase in atheromatous lesions in the aortic sinus as well as
increases in the levels of serum monocyte chemoattractant protein 1. Further, P.
gingivalis injection significantly enhanced the formation of atherosclerotic
plaque, and increased CRP and inflammatory cytokine levels, in mice fed the HFD,
although no further increase in LDL was observed. CONCLUSION: These results
suggest that bacteremia-induced by repeated injection with P. gingivalis
accelerates atherosclerosis in normal C57BL/6 mice by initiating inflammation,
and is therefore implicated in chronic infection-related pathogenicity.
PMID- 22047043
TI - Dynamic structure factor for large aggregate clusters with internal motions: a
self-consistent light-scattering study on conjugated polymer solutions.
AB - The aggregation properties of a standard conjugated polymer, poly(2-methoxy-5-(2'
ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV), in two distinct solvents
(chloroform and toluene) and a range of polymer concentrations (c = 0.1-3 mg/mL)
have been unequivocally resolved using combined dynamic and static light
scatterings (DLS/SLS). The prime challenges for analyzing this peculiar,
practically important, solution system arise from the wide size distribution and
unknown aggregate morphology, as well as pronounced interferences between
translational and internal motions of aggregate clusters of considerably varying
size. To cope with these central difficulties, we propose a self-consistent
formulation for analyzing the dynamic structure factor in DLS experiment by
extending an existing theory on free-draining bead-spring chains that explicitly
accounts for internal fluctuations, along with two candidate form factors on
Gaussian coil and rigid sphere, respectively, serving as two limiting cases to be
discriminated in combined DLS and SLS measurements. Given that no accessibility
to ultrasmall angular resolutions is a prerequisite, the suggested protocol can
readily be carried out in conventional light-scattering apparatus. The present
analyses unanimously support the rigid-sphere form factor in describing the
entire set of light-scattering data on MEH-PPV solutions, differing from early
small-angle neutron/X-ray scattering interpretations suggesting certain 2D
fractal structures for the aggregation network. Scrutiny into the interior
dynamics of aggregate clusters further disclosed that the segmental motions are
noticeably more suppressed than for usual, nonaggregated polymer solutions, and
no existing theories based on the bead-spring picture can yet capture the
observed scaling behavior as manifested by the present data. Accordingly, we
report several first-revealed properties of MEH-PPV solutions on the aggregate
morphology, the size distribution (and mean size), mean aggregation number, and
interior segmental dynamics, which serve as valuable information for linking
solution properties with those for dried thin films in contemporary applications
with conducting conjugated polymers.
PMID- 22047044
TI - Correspondence between salivary proteomic pattern and clinical course in primary
Sjogren syndrome and non-Hodgkin's lymphoma: a case report.
AB - BACKGROUND: In the last years human proteomic has represented a promising tool to
promote the communication between basic and clinical science. METHODS: To explore
the correspondence between salivary proteomic profile and clinical response,
herein, we used a proteomic approach to analyse the whole saliva of a patient
with primary Sjogren's Syndrome (pSS) and non-Hodgkin's-MALT type parotid
lymphoma before, during and after a standard treatment with cyclophosphamide
(CTX) and rituximab (RTX). To identify any discriminatory therapeutic salivary
biomarker patient's whole saliva was collected at the baseline, after the fourth
infusion of rituximab, and on remission and analysed combining two-dimensional
electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry. RESULTS: Proteomic
results obtained from the comparison of salivary samples indicated several
qualitative and quantitative modifications in the salivary expression of putative
albumin, immunoglobulin J chain, Ig kappa chain C region, alpha-1-antitrypsin,
haptoglobin and Ig alpha-1 chain C region. CONCLUSION: This study suggests that
clinical and functional changes of the salivary glands driven by autoimmune and
lymphoproliferative processes might be reflected in patients' whole saliva
proteins, shedding new light on the potential usefulness of salivary proteomic
analysis in the identification of prognostic and therapeutic biomarkers for
patients with pSS and non Hodgkin's lymphomas.
PMID- 22047045
TI - Multivariate modelling with (1)H NMR of pleural effusion in murine cerebral
malaria.
AB - BACKGROUND: Cerebral malaria is a clinical manifestation of Plasmodium falciparum
infection. Although brain damage is the predominant pathophysiological
complication of cerebral malaria (CM), respiratory distress, acute lung injury,
hydrothorax/pleural effusion are also observed in several cases. Immunological
parameters have been assessed in pleural fluid in murine models; however there
are no reports of characterization of metabolites present in pleural effusion.
METHODS: 1H NMR of the sera and the pleural effusion of cerebral malaria infected
mice were analyzed using principal component analysis, orthogonal partial least
square analysis, multiway principal component analysis, and multivariate curve
resolution. RESULTS: It has been observed that there was 100% occurrence of
pleural effusion (PE) in the mice affected with CM, as opposed to those are non
cerebral and succumbing to hyperparasitaemia (NCM/HP). An analysis of 1H NMR and
SDS-PAGE profile of PE and serum samples of each of the CM mice exhibited a
similar profile in terms of constituents. Multivariate analysis on these two
classes of biofluids was performed and significant differences were detected in
concentrations of metabolites. Glucose, creatine and glutamine contents were high
in the PE and lipids being high in the sera. Multivariate curve resolution
between sera and pleural effusion showed that changes in PE co-varied with that
of serum in CM mice. The increase of glucose in PE is negatively correlated to
the glucose in serum in CM as obtained from the result of multiway principal
component analysis. CONCLUSIONS: This study reports for the first time, the
characterization of metabolites in pleural effusion formed during murine cerebral
malaria. The study indicates that the origin of PE metabolites in murine CM may
be the serum. The loss of the components like glucose, glutamine and creatine
into the PE may worsen the situation of patients, in conjunction with the
enhanced glycolysis, glutaminolysis and increased activity of creatine
phophokinase which are already reported characteristic pathophysiological
features of malaria.
PMID- 22047046
TI - Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine
surgery for degenerative spinal stenosis with instability: a retrospective case
control study.
AB - BACKGROUND: Degenerative spinal stenosis and instability requiring multilevel
spine surgery has been associated with large blood losses. Factors that affect
perioperative blood loss include time of surgery, surgical procedure, patient
height, combined anterior/posterior approaches, number of levels fused, blood
salvage techniques, and the use of anti-fibrinolytic medications. This study was
done to evaluate the efficacy of tranexamic acid in reducing blood loss in spine
surgery. METHODS: This retrospective case control study includes 97 patients who
had to undergo surgery because of degenerative lumbar spinal stenosis and
instability. All operations included spinal decompression, interbody fusion and
posterior instrumentation (4-5 segments). Forty-six patients received 1 g
tranexamic acid intravenous, preoperative and six hours and twelve hours
postoperative; 51 patients without tranexamic acid administration were evaluated
as a control group. Based on the records, the intra- and postoperative blood
losses were measured by evaluating the drainage and cell saver systems 6, 12 and
24 hours post operation. Additionally, hemoglobin concentration and platelet
concentration were reviewed. Furthermore, the number of red cell transfusions
given and complications associated with tranexamic acid were assessed. RESULTS:
The postoperative hemoglobin concentration demonstrated a statistically
significant difference with a p value of 0.0130 showing superiority for
tranexamic acid use (tranexamic acid group: 11.08 g/dl, SD: 1.68; control group:
10.29 g/dl, SD: 1.39). The intraoperative cell saver volume and drainage volume
after 24 h demonstrated a significant difference as well, which indicates a less
blood loss in the tranexamic acid group than the control group. The postoperative
drainage volume at12 hours showed no significant differences; nor did the
platelet concentration Allogenic blood transfusion (two red cell units) was
needed for eight patients in the tranexamic acid group and nine in the control
group because of postoperative anemia. Complications associated with the
administration of tranexamic acid, e.g. renal failure, deep vein thrombosis or
pulmonary embolism did not occur. CONCLUSIONS: This study suggests a less blood
loss when administering tranexamic acid in posterior lumbar spine surgery as
demonstrated by the higher postoperative hemoglobin concentration and the less
blood loss. But given the relatively small volume of blood loss in the patients
of this study it is underpowered to show a difference in transfusion rates.
PMID- 22047047
TI - Factors associated with paradoxical immune response to antiretroviral therapy in
HIV infected patients: a case control study.
AB - BACKGROUND: A paradoxical immunologic response (PIR) to Highly Active
Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell
count improvement, has been reported in the literature as 8 to 42%, around 15% in
most instances. The present study aims to determine, in a cohort of HIV infected
patients in Brazil, what factors were independently associated with such a
discordant response to HAART. METHODS: A case-control study (1:4) matched by
gender was conducted among 934 HIV infected patients on HAART in Brazil. CASES:
patients with PIR, defined as CD4 < 350 cells/mm(3) (hazard ratio for AIDS or
death of at least 8.5) and undetectable HIV viral load on HAART for at least one
year. CONTROLS: similar to cases, but with CD4 counts >= 350 cells/mm(3).
Eligibility criteria were applied. Data were collected from medical records using
a standardized form. Variables were introduced in a hierarchical logistic
regression model if a p-value < 0.1 was determined in a bivariate analysis.
RESULTS: Among 934 patients, 39 cases and 160 controls were consecutively
selected. Factors associated with PIR in the logistic regression model were:
total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR
0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI
95%: 0.94-0.99). CONCLUSIONS: PIR seems to be related to a delay in the
management of immunodeficient patients, as shown by its negative association with
nadir CD4-count. Strategies should be implemented to avoid such a delay and
improve the adherence to HAART as a way to implement concordant responses.
PMID- 22047048
TI - Type-2 isopentenyl diphosphate isomerase: evidence for a stepwise mechanism.
AB - Isopentenyl diphosphate isomerase (IDI) catalyzes the interconversion of
isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). These two
molecules are the building blocks for construction of isoprenoid carbon skeletons
in nature. Two structurally unrelated forms of IDI are known. A variety of
studies support a proton addition/proton elimination mechanism for both enzymes.
During studies with Thermus thermophilus IDI-2, we discovered that the olefinic
hydrogens of a vinyl thiomethyl analogue of isopentenyl diphosphate exchanged
with solvent when the enzyme was incubated with D(2)O without concomitant
isomerization of the double bond. These results suggest that the enzyme-catalyzed
isomerization reaction is not concerted.
PMID- 22047049
TI - Mossbauer and EPR study of iron in vacuoles from fermenting Saccharomyces
cerevisiae.
AB - Vacuoles were isolated from fermenting yeast cells grown on minimal medium
supplemented with 40 MUM (57)Fe. Absolute concentrations of Fe, Cu, Zn, Mn, Ca,
and P in isolated vacuoles were determined by ICP-MS. Mossbauer spectra of
isolated vacuoles were dominated by two spectral features: a mononuclear
magnetically isolated high-spin (HS) Fe(III) species coordinated primarily by
hard/ionic (mostly or exclusively oxygen) ligands and superparamagnetic Fe(III)
oxyhydroxo nanoparticles. EPR spectra of isolated vacuoles exhibited a g(ave) ~
4.3 signal typical of HS Fe(III) with E/D ~ 1/3. Chemical reduction of the HS
Fe(III) species was possible, affording a Mossbauer quadrupole doublet with
parameters consistent with O/N ligation. Vacuolar spectral features were present
in whole fermenting yeast cells; however, quantitative comparisons indicated that
Fe leaches out of vacuoles during isolation. The in vivo vacuolar Fe
concentration was estimated to be ~1.2 mM while the Fe concentration of isolated
vacuoles was ~220 MUM. Mossbauer analysis of Fe(III) polyphosphate exhibited
properties similar to those of vacuolar Fe. At the vacuolar pH of 5, Fe(III)
polyphosphate was magnetically isolated, while at pH 7, it formed nanoparticles.
This pH-dependent conversion was reversible. Fe(III) polyphosphate could also be
reduced to the Fe(II) state, affording similar Mossbauer parameters to that of
reduced vacuolar Fe. These results are insufficient to identify the exact
coordination environment of the Fe(III) species in vacuoles, but they suggest a
complex closely related to Fe(III) polyphosphate. A model for Fe trafficking
into/out of yeast vacuoles is proposed.
PMID- 22047050
TI - The impact of initiating biphasic human insulin 30 therapy in type 2 diabetes
patients after failure of oral antidiabetes drugs.
AB - BACKGROUND: The present study evaluated the efficacy of biphasic human insulin 30
(BHI 30) in type 2 diabetes patients who had failed in therapy with two or more
oral antidiabetes drugs (OADs). METHODS: This open-label, nonrandomized, 4-month,
multicenter, clinical observational study was conducted in Shanghai, China. A
total of 660 insulin-naive type 2 diabetes patients with poor glycemic control
(glycosylated hemoglobin [HbA1c] >=7.5%), despite treatment with two or more OADs
for more than 6 months, were recruited and received BHI 30 monotherapy or BHI 30
plus OAD(s) (metformin only, alpha-glucosidase inhibitor only, or both). RESULTS:
Among the 660 subjects, 644 completed the 4-month study. At the end of the study,
the median level of HbA1c decreased by 2.0% (from 9.1% to 7.0%) in the BHI 30
monotherapy group and also 2.0% (from 9.5% to 7.3%) in the BHI 30 plus OAD group.
More patients achieved the HbA1c <7.0% target in the BHI 30 monotherapy group
than in the BHI 30 plus OAD(s) group (47.9% vs. 35.3%, P=0.002). Compared with
the expenses of the prior treatment strategy, the median daily cost decreased by
39.8% (4.5 yuan, Chinese RMB) at the end point in the BHI 30 monotherapy group
but increased by 20.0% (2.2 yuan) in the BHI 30 plus OAD(s) group (P<0.0001).
Moreover, patients in the BHI 30 plus OAD(s) group had fewer minor hypoglycemic
episodes than in the BHI 30 monotherapy group (mean of 1.06 vs. 2.77 per patient
per year, P<0.0001). CONCLUSIONS: Short-term BHI 30 therapy can improve glycemic
control in insulin-naive type 2 diabetes patients after failure of two or more
OADs. With higher baseline glucose level, the BHI 30 plus OAD(s) group had lower
pharmacoeconomic efficacy than the BHI 30 monotherapy group despite having fewer
hypoglycemia events.
PMID- 22047051
TI - A comparison of average daily risk range scores for young children with type 1
diabetes mellitus using continuous glucose monitoring and self-monitoring data.
AB - BACKGROUND: Young children with type 1 diabetes are vulnerable to glycemic
excursion. Continuous glucose monitoring (CGM), combined with variability
statistics, can offer a richer and more complete picture of glycemic variability
in young children. In particular, we present data for the Average Daily Risk
Range (ADRR) and compare ADRR scores calculated using CGM versus self-monitoring
of blood glucose (SMBG) data for young children. METHODS: CGM and SMBG data from
48 young children with type 1 diabetes (mean age, 5.1 years) were used to
calculate two separate ADRR scores, using SMBG data (ADRRs) and CGM data (ADRRc),
for each child. Additionally, we calculated mean amplitude of glycemic excursion
(MAGE) scores for children to examine the concurrent validity of the ADRRs and
ADRRc. RESULTS: Young children's mean ADRRc score was significantly greater than
their ADRRs score (55+/-12 and 46+/-11, respectively; P<0.001). In addition, 74%
of the time the children's ADRRc score reflected greater variability risk than
their ADRRs score. Examining the concurrent validity, children's ADRRc scores
correlated positively with MAGE scores calculated using their CGM and SMBG data,
whereas their ADRRs scores only correlated with MAGE scores calculated using
SMBG. CONCLUSIONS: ADRR scores generated for young children with type 1 diabetes
demonstrate a high risk for glucose variability, but ADRR scores generated from
CGM data may provide a more sensitive measure of variability than ADRR scores
generated from SMBG. In young children with type 1 diabetes, ADRR scores
calculated from CGM data may be superior to scores calculated from SMBG for
measuring risk of excursion.
PMID- 22047052
TI - Development of a novel three-dimensional, automatable and integrated bioprocess
for the differentiation of embryonic stem cells into pulmonary alveolar cells in
a rotating vessel bioreactor system.
AB - Application of stem cells for cell therapy of respiratory diseases is a
developing field. We have previously established several protocols for the
differentiation of embryonic stem cells (ESC) into alveolar epithelial cells,
which require a high degree of operator interference and result in a low yield of
target cells. Herein, we have shown that, by provision of a medium conditioned
using A549 cells and by integration of classic steps of ESC differentiation into
a single step through encapsulation in hydrogels (three-dimensional) and culture
in a rotary bioreactor, murine ESC (mESC) could be directed to differentiate into
distal respiratory epithelial cells. Type I and II pneumocytes (with a yield of
50% for type II) and Clara cells were demonstrated by the expression of aquaporin
5, surfactant protein C, and Clara cell secretory protein, respectively. We
identified target cells as early as day 5 of culture and stably maintained our
differentiated cells in vitro for 100 days. Electron microscopy demonstrated
microvilli and intracellular lamellar bodies (LB), and fluorescent staining
confirmed the active process of exocytosis of these LB in differentiated type II
cells. When these cells were decapsulated and cultured in static conditions in
flask cultures (two-dimensional), they retained their characteristic type II
phenotype and morphology. In conclusion, our protocol offers integrated
bioprocessing, shorter time of differentiation, lower cost, no use of growth
factors, high reproducibility, and high phenotypic and functional stability, as
well as being amenable to automation and being scalable, which would move this
field closer to future clinical applications.
PMID- 22047053
TI - NIST gold nanoparticle reference materials do not induce oxidative DNA damage.
AB - One primary challenge in nanotoxicology studies is the lack of well-characterised
nanoparticle reference materials which could be used as positive or negative
nanoparticle controls. The National Institute of Standards and Technology (NIST)
has developed three gold nanoparticle (AuNP) reference materials (10, 30 and 60
nm). The genotoxicity of these nanoparticles was tested using HepG2 cells and
calf-thymus DNA. DNA damage was assessed based on the specific and sensitive
measurement of four oxidatively-modified DNA lesions (8-hydroxy-2'
deoxyguanosine, 8-hydroxy-2'-deoxyadenosine, (5'S)-8,5'-cyclo-2'-deoxyadenosine
and (5'R)-8,5'-cyclo-2'-deoxyadenosine) using liquid chromatography/tandem mass
spectrometry. Significantly elevated, dose-dependent DNA damage was not detected
at concentrations up to 0.2 MUg/ml, and free radicals were not detected using
electron paramagnetic resonance spectroscopy. These data suggest that the NIST
AuNPs could potentially serve as suitable negative-control nanoparticle reference
materials for in vitro and in vivo genotoxicity studies. NIST AuNPs thus hold
substantial promise for improving the reproducibility and reliability of
nanoparticle genotoxicity studies.
PMID- 22047054
TI - A novel class of small molecule inhibitors of HDAC6.
AB - Histone deacetylases (HDACs) are a family of enzymes that play significant roles
in numerous biological processes and diseases. HDACs are best known for their
repressive influence on gene transcription through histone deacetylation. Mapping
of nonhistone acetylated proteins and acetylation-modifying enzymes involved in
various cellular pathways has shown protein acetylation/deacetylation also plays
key roles in a variety of cellular processes including RNA splicing, nuclear
transport, and cytoskeletal remodeling. Studies of HDACs have accelerated due to
the availability of small molecule HDAC inhibitors, most of which contain a
canonical hydroxamic acid or benzamide that chelates the metal catalytic site. To
increase the pool of unique and novel HDAC inhibitor pharmacophores, a
pharmacological active compound screen was performed. Several unique HDAC
inhibitor pharmacophores were identified in vitro. One class of novel HDAC
inhibitors, with a central naphthoquinone structure, displayed a selective
inhibition profile against HDAC6. Here we present the results of a unique class
of HDAC6 inhibitors identified using this compound library screen. In addition,
we demonstrated that treatment of human acute myeloid leukemia cell line MV4-11
with the selective HDAC6 inhibitors decreases levels of mutant FLT-3 and
constitutively active STAT5 and attenuates Erk phosphorylation, all of which are
associated with the inhibitor's selective toxicity against leukemia.
PMID- 22047055
TI - Inhibition of development of Shiga toxin-converting bacteriophages by either
treatment with citrate or amino acid starvation.
AB - OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) are pathogenic strains,
whose virulence depends on induction of Shiga toxin-converting prophages and
their subsequent lytic development. We explored which factors or conditions could
inhibit development of these phages, potentially decreasing virulence of STEC.
MATERIALS AND METHODS: Lytic development of Shiga toxin-converting bacteriophages
was monitored after mitomycin C-provoked prophage induction under various
conditions. Phage DNA replication efficiency was assessed by measurement of DNA
amount in cells using quantitative polymerase chain reaction. RESULTS: We
demonstrated that the use of citrate delayed Shiga toxin-converting phage
development after prophage induction. This effect was independent on efficiency
of prophage induction and phage DNA replication. However, an excess of glucose
reversed the effect of citrate. Amino acid starvation prevented the phage
development in bacteria both able and unable to induce the stringent response.
CONCLUSIONS: Lytic development of Shiga toxin-converting bacteriophages can be
inhibited by either the presence of citrate or amino acid starvation. We suggest
that the inhibition caused by the latter condition may be due to a block in
prophage induction or phage DNA replication or both. APPLICATIONS: Our findings
may facilitate development of procedures for treatment of STEC-infected patients.
PMID- 22047056
TI - Evaluation of a multiplex real-time polymerase chain reaction for the
quantification of Escherichia coli O157 in cattle feces.
AB - Cattle are asymptomatic reservoirs for Escherichia coli O157, a major foodborne
pathogen. The organism generally colonizes the hindgut of cattle and is shed in
the feces at low concentrations. The objective of this research was to evaluate a
multiplex, real-time polymerase chain reaction (mqPCR) assay for quantification
of E. coli O157 in cattle feces using stx1, stx2, and rfbE gene targets. Primer
efficiency and analytical sensitivity of the assay were evaluated with a single
or pooled (five strain) culture of E. coli O157. In pure culture, the minimum
detection limit of the assay was 1.4*10(3) CFU/mL and 3.6*10(3) CFU/mL for the
single and five-strain mixture of E. coli O157, respectively. Diagnostic
sensitivity was analyzed using DNA extracted from cattle feces spiked with E.
coli O157. In feces spiked with the pooled mixture of five E. coli O157 strains,
the minimum detection limit was 3.6*10(4) CFU/g. We also evaluated the assay with
feces from cattle experimentally inoculated with E. coli O157 by comparing the
results to a culture-based method. For the majority of samples tested, the
concentration of E. coli O157 detected by the real-time and culture methods was
within one log difference. However, the assay could only be evaluated for cattle
shedding high concentrations of E. coli O157. In conclusion, the mqPCR
quantifying E. coli O157 in cattle feces using stx1, stx2, and rfbE gene targets
may have use in detecting and quantifying super shedders, but is not applicable
for quantification in animals shedding low concentrations (10(2) to 10(3) CFU/g
feces).
PMID- 22047057
TI - A regional Salmonella enterica serovar Typhimurium outbreak associated with raw
beef products, The Netherlands, 2010.
AB - Between April and May 2010, several medical microbiological laboratories in the
Netherlands notified a total of 90 cases of Salmonella enterica serovar
Typhimurium with the same antibiogram type (resistant for ampicillin,
tetracycline, and co-trimoxazol) and the same multiple locus variable number
tandem repeats analysis pattern (03-16-09-NA-311) or single locus variants. Date
of illness onset ranged from end of March to mid-May with a peak in the second
week of April. Almost half of the cases were hospitalized. Cases completed a
questionnaire about food items and other risk factors in the 7 days before
illness onset. A matched case-control study was performed. Consumption of
"ossenworst" (matched odds ratio 48.2 [95% confidence interval (CI): 3.9-595.9])
and filet americain (8.5 [95% CI: 1.0-73.6]) were found to be significant risk
factors for illness. Eighty percent of the cases had eaten at least one or both
raw meat products. The producer of the ground beef that was used to produce the
"ossenworst" was identified, but no microbiological evidence was found. Consumers
should be made more aware of the presence of raw meat in ready-to-eat products
and of the potential risk in eating these products. Vulnerable persons such as
young children, elderly, and persons with poor health should be discouraged from
eating these products. Detection of this outbreak was mainly based on the
antibiogram pattern that had identified possible cases 10 days before detailed
typing results from the reference laboratory became available, thus facilitating
early case findings.
PMID- 22047058
TI - An emerging role for the nuclear localization of maspin in the suppression of
tumor progression and metastasis.
AB - Maspin, a member of the serpin family of serine protease inhibitors, was
originally identified as a tumor suppressor that is expressed in normal mammary
epithelial cells but is reduced or absent in breast carcinomas. Early enthusiasm
for maspin as a biomarker for disease progression has been tempered by clinical
data that associates maspin with favourable outcomes in some studies and poor
prognosis in others. Here, we review all of the published clinical studies for
maspin in breast and ovarian cancers and propose that the apparent discordance
between clinical reports is a consequence of differential cellular distribution
of maspin. Indeed, it was thought that an extracellular pool of maspin possessed
tumor suppressor activity, acting by inhibiting migration and increasing cell
adhesion. Recent evidence from our group and others indicates, however, that the
nuclear localization of maspin in cancer cells is necessary for its tumor
suppressor activity. We provide additional data here to demonstrate that nuclear
localized maspin binds to chromatin and is required to effectively prevent cells
from metastasizing. Our knowledge of other serpins that localize to the nucleus
should help to inform future studies of nuclear maspin. Elucidation of the
molecular mechanisms regulating the localization and activities of maspin should
pave the way for the development of improved diagnostics and therapies for
cancer.
PMID- 22047059
TI - Cognitive effects of chemotherapy-induced menopause in breast cancer.
AB - This study examined whether chemotherapy-induced menopause affects cognitive
functioning in women with early breast cancer. The neuropsychological performance
of 121 breast cancer patients (age M=49.62, SD=8.11, range=25.25-67.92) treated
with chemotherapy was assessed pre-chemotherapy, as well as 1, 6, and 18 months
post-chemotherapy completion. Linear mixed modeling was used to evaluate the
data. Type of menopause (pre, chemotherapy-induced, and post menopause) was found
to significantly interact with cognitive performance on two cognitive variables.
Specifically, chemotherapy-induced menopausal women did not show any significant
changes in performance on an abstract reasoning task, while the pre-menopausal
and post-menopausal groups significantly improved over time. A significant
interaction on a test of finger dexterity and coordination was also found,
although inspection of the results indicated that this was due to a significant
improvement in the pre-menopausal groups at 6 months post chemotherapy. After
chemotherapy most cognitive variables showed improvements over time, although two
indicators of verbal memory showed significant declines immediately after
chemotherapy, with improvement by 18 months post completion. The current study
found little evidence to suggest that chemotherapy-induced menopause broadly
affects cognitive functioning after treatment administration. However, longer
follow-up assessments are warranted to assess the long-term effects of combined
chemotherapy and endocrine treatment.
PMID- 22047060
TI - Quality assessment of the registration of vulvar and vaginal premalignant lesions
at the Cancer Registry of Norway.
AB - BACKGROUND: A crucial factor concerning the utility of Cancer Registries is the
data quality with respect to comparability, completeness, validity and
timeliness. However, the data quality of the registration of premalignant lesions
has rarely been addressed. High grade vulvar intraepithelial neoplasia (VIN) and
vaginal intraepithelial neoplasia (VaIN) are premalignant lesions which may
develop into cancer, and are often associated with infection with the human
papillomarvirus (HPV). The aim was to evaluate the quality of registration of VIN
and VaIN at the Cancer Registry of Norway (CRN). MATERIAL AND METHODS: We re
collected all notifications with high grade VIN and VaIN diagnoses during 2002 to
2007 from pathology laboratories, and compared these to the data in the CRN
database so as to quantitatively measure the completeness, validity and
timeliness of the data. RESULTS: Over the period 2002 to 2007 we estimated the
completeness of the 1556 VIN and 297 VaIN notifications to be 95.0% and 92.9%,
respectively. The original and reabstracted topography codes showed major
discrepancies for 12 of 642 (1.9%) VIN and 7 of 128 (5.5%) VaIN notifications.
The original and reabstracted morphology codes for VIN and VaIN were identical
for 724 out of 814 notifications. Sixteen notifications had a major discrepancy.
For the period 2002 to 2007 the median time elapsed between date of diagnosis and
date of registration were 436 and 441 days for VIN and VaIN cases, respectively.
DISCUSSION: Based on the present analysis of the comparability, completeness,
validity and timeliness of premalignant lesions of vulva and vagina, we conclude
that the Cancer Registry of Norway is able to monitor such premalignant lesions
satisfactorily.
PMID- 22047061
TI - Initial recombination in the track of heavy charged particles: numerical solution
for air filled ionization chambers.
AB - INTRODUCTION: Modern particle therapy facilities enable sub-millimeter precision
in dose deposition. Here, also ionization chambers (ICs) are used, which requires
knowledge of the recombination effects. Up to now, recombination is corrected
using phenomenological approaches for practical reasons. In this study the effect
of the underlying dose distribution on columnar recombination, a quantitative
model for initial recombination, is investigated. MATERIAL AND METHODS: Jaffe's
theory, formulated in 1913 quantifies initial recombination by elemental
processes, providing an analytical (closed) solution. Here, we investigate the
effect of the underlying charged carrier distribution around a carbon ion track.
The fundamental partial differential equation, formulated by Jaffe, is solved
numerically taking into account more realistic charge carrier distributions by
the use of a computer program (Gascoigne 3D). The investigated charge carrier
distributions are based on track structure models, which follow a 1/r(2) behavior
at larger radii and show a constant value at small radii. The results of the
calculations are compared to the initial formulation and to data obtained in
experiments using carbon ion beams. RESULTS: The comparison between the
experimental data and the calculations shows that the initial approach made by
Jaffe is able to reproduce the effects of initial recombination. The amorphous
track structure based charge carrier distribution does not reproduce the
experimental data well. A small additional correction in the assessment of the
saturation current or charge is suggested by the data. CONCLUSION: The
established model of columnar recombination reproduces the experimental data
well, whereas the extensions using track structure models do not show such an
agreement. Additionally, the effect of initial recombination on the saturation
curve (i.e. Jaffe plot) does not follow a linear behavior as suggested by current
dosimetry protocols, therefore higher order corrections (such as the investigated
ones) might be necessary.
PMID- 22047062
TI - D2-symmetric dirhodium catalyst derived from a 1,2,2
triarylcyclopropanecarboxylate ligand: design, synthesis and application.
AB - Dirhodium tetrakis-(R)-(1-(4-bromophenyl)-2,2-diphenylcyclopropanecarboxylate)
(Rh(2)(R-BTPCP)(4)) was found to be an effective chiral catalyst for
enantioselective reactions of aryl- and styryldiazoacetates. Highly
enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements
and a combined C-H functionalization/Cope rearrangement were achieved using
Rh(2)(R-BTPCP)(4) as catalyst. The advantages of Rh(2)(R-BTPCP)(4) include its
ease of synthesis, its tolerance to the size of the ester group in the
styryldiazoacetates, and its compatibility with dichloromethane as solvent.
Computational studies suggest that the catalyst adopts a D(2)-symmetric
arrangement, but when the carbenoid binds to the catalyst, two of the p
bromophenyl groups on the ligands rotate outward to make room for the carbenoid
and the approach of the substrate to the carbenoid.
PMID- 22047066
TI - Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary
ammonium palmitoyl glycol chitosan nanoparticles.
AB - As 95% of all prescriptions are for orally administered drugs, the issue of oral
absorption is central to the development of pharmaceuticals. Oral absorption is
limited by a high molecular weight (>500 Da), a high log P value (>2.0) and low
gastrointestinal permeability. We have designed a triple action nanomedicine from
a chitosan amphiphile: quaternary ammonium palmitoyl glycol chitosan (GCPQ),
which significantly enhances the oral absorption of hydrophobic drugs (e.g.,
griseofulvin and cyclosporin A) and, to a lesser extent, the absorption of
hydrophilic drugs (e.g., ranitidine). The griseofulvin and cyclosporin A C(max)
was increased 6- and 5-fold respectively with this new nanomedicine. Hydrophobic
drug absorption is facilitated by the nanomedicine: (a) increasing the
dissolution rate of hydrophobic molecules, (b) adhering to and penetrating the
mucus layer and thus enabling intimate contact between the drug and the
gastrointestinal epithelium absorptive cells, and (c) enhancing the transcellular
transport of hydrophobic compounds. Although the C(max) of ranitidine was
enhanced by 80% with the nanomedicine, there was no appreciable opening of tight
junctions by the polymer particles.
PMID- 22047067
TI - Childhood chronic anterior uveitis associated with vernal keratoconjunctivitis
(VKC): successful treatment with topical tacrolimus. Case series.
AB - Uveitis treatment involves topical corticosteroids along with cycloplegic
mydriatics. Particularly severe cases may require systemic corticosteroids and
immunosuppressive drugs. Vernal keratoconjunctivitis (VKC) treatment consists of
a brief period of topical corticosteroids and/or cyclosporine. In patients
refractory to traditional treatment, the use of 0.1% topical ophtalmic FK- 506
(tacrolimus) ointment has been occasionally reported.This is the first report of
the coexistence of uveitis and VKC. The documented response to topical tacrolimus
eyedrop of uveitis and VKC is also of interest, in particular since to our
knowledge there are no published reports on its clinical use in uveitis.
PMID- 22047068
TI - Catalytic enantioselective intermolecular cycloaddition of diazodiketoester
derived carbonyl ylides with indoles using chiral dirhodium(II) carboxylates.
AB - The first example of enantioselective intermolecular cycloaddition of carbonyl
ylides with indoles is described. The cycloaddition of five- and six-membered
carbonyl ylides derived from diazodiketoesters with N-methylindoles under
catalysis by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate],
Rh(2)(S-TCPTTL)(4), gave cycloadducts in high yields and with high levels of
enantioselectivity (up to 99% ee) as well as excellent exo diastereoselectivity.
PMID- 22047069
TI - Retargeted clostridial neurotoxins as novel agents for treating chronic diseases.
AB - Botulinum neurotoxin (BoNT) A and B are used to treat neuropathic disorders; if
retargeted, these agents could be used to treat medical conditions that involve
secretion from nonneuronal cells. Here, we report novel strategies for
successfully retargeting BoNTs, and also tetanus neurotoxin (TeNT), to primary
human blood monocyte-derived macrophages where BoNT/B inhibited the release of
tumor necrosis factor-alpha, a cytokine that plays a key role in inflammation.
Furthermore, mice treated with retargeted BoNT/B exhibited a significant
reduction in macrophage (MPhi) recruitment, indicating that these toxins can be
used to treat chronic inflammation.
PMID- 22047071
TI - A randomised controlled crossover trial evaluating Television Assisted Prompting
(TAP) for adults with acquired brain injury.
AB - Assistive technologies for cognition (ATC) provide an effective means to
compensate for prospective memory failures among adults with acquired brain
injury (ABI; de Joode, van Heugten, Verhey, & van Boxtel, 2010 ; Sohlberg et
al., 2007 ). This study evaluated a novel ATC device, the Television Assisted
Prompting (TAP) system, which provides audiovisual reminders at scheduled
prospective times on a person's home television. A randomised, controlled
crossover design evaluated task completion for two preferred, two non-preferred,
and two structured experimental tasks among 23 adults with ABI between two
conditions: TAP prompting or typical (TYP) practice, without TAP reminders. Main
outcomes showed a significant advantage of prospective memory prompting (72%
completion) over no prompting (43% completion) and higher task completion with
TAP prompting for researcher-assigned experimental tasks (81%) compared to self
selected preferred (68%) or non-preferred (68%) tasks. Results are discussed in
the context of ATC efficacy to support prospective memory prompting following
ABI, with contributions and future directions for continued investigation of
customisation of prompts to maximise task completion.
PMID- 22047072
TI - Statement of retraction. An evaluation of the association of malnutrition with
nosocomial infections in elderly patients.
PMID- 22047073
TI - Effects of Erxian decoction, a Chinese medicinal formulation, on serum lipid
profile in a rat model of menopause.
AB - BACKGROUND: The prevalence and risk of cardiovascular disease increase after
menopause in correlation with the progression of abnormality in the serum lipid
profile and the deprivation of estrogen. Erxian decoction (EXD), a Chinese
medicinal formulation for treating menopausal syndrome, stimulates ovarian
estrogen biosynthesis. This study investigates whether EXD improves the serum
lipid profile in a menopausal rat model. METHODS: Twenty-month-old female Sprague
Dawley rats were treated with EXD and its constituent fractions. Premarin was
administered for comparison. After eight weeks of treatment, rats were sacrificed
and the serum levels of total cholesterol, triglyceride, high-density-lipoprotein
cholesterol and low-density-lipoprotein cholesterol were determined. The hepatic
protein levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase and low-density
lipoprotein receptor were assessed with Western blot. RESULTS: The serum levels
of total cholesterol and low-density-lipoprotein cholesterol were significantly
lower in the EXD-treated group than in the constituent fractions of EXD or
premarin groups. However, the serum levels of triglyceride and high-density
lipoprotein cholesterol were not significantly different from the control groups.
Results from Western blot suggest that EXD significantly down-regulated the
protein level of 3-hydroxy-3-methyl-glutaryl-CoA reductase and up-regulated low
density-lipoprotein receptor. Conclusion EXD improves serum lipid profile in a
menopausal rat model through the suppression of the serum levels of total
cholesterol and low-density-lipoprotein cholesterol, possibly through the down
regulation of the 3-hydroxy-3-methyl-glutaryl-CoA and up-regulation of the low
density-lipoprotein receptor.
PMID- 22047074
TI - Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases.
AB - Unsaturated glucuronyl hydrolases (UGLs) from GH family 88 of the CAZy
classification system cleave a terminal unsaturated sugar from the
oligosaccharide products released by extracellular bacterial polysaccharide
lyases. This pathway, which is involved in extracellular bacterial infection, has
no equivalent in mammals. A novel mechanism for UGL has previously been proposed
in which the enzyme catalyzes hydration of a vinyl ether group in the substrate,
with subsequent rearrangements resulting in glycosidic bond cleavage. However,
clear evidence for this mechanism has been lacking. In this study, analysis of
the products of UGL-catalyzed reactions in water, deuterium oxide, and dilute
methanol in water, in conjunction with the demonstration that UGL rapidly cleaves
thioglycosides and glycosides of inverted anomeric configuration (substrates that
are resistant to hydrolysis by classical glycosidases), provides strong support
for this new mechanism. A hydration-initiated process is further supported by the
observed UGL-catalyzed hydration of a C-glycoside substrate analogue. Finally,
the observation of a small beta-secondary kinetic isotope effect suggests a
transition state with oxocarbenium ion character, in which the hydrogen at carbon
4 adopts an axial geometry. Taken together, these observations validate the novel
vinyl ether hydration mechanism and are inconsistent with either inverting or
retaining direct hydrolase mechanisms at carbon 1.
PMID- 22047075
TI - SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in
Drosophila melanogaster.
AB - BACKGROUND: The SWI/SNF chromatin remodeling factors have the ability to remodel
nucleosomes and play essential roles in key developmental processes. SWI/SNF
complexes contain one subunit with ATPase activity, which in Drosophila
melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have
been attributed to its influence on chromatin structure and transcription
regulation, but recent observations have revealed that the levels of Brm affect
the relative abundances of transcripts that are formed by alternative splicing
and/or polyadenylation of the same pre-mRNA. RESULTS: We have investigated
whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is
mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of
depleting individual SWI/SNF subunits on pre-mRNA processing throughout the
genome, and we have identified a subset of transcripts that are affected by
depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion
of different subunits targets a subset of common transcripts suggests that the
SWI/SNF complex is responsible for the effects observed on pre-mRNA processing
when knocking down Brm. We have also depleted Brm in larvae and we have shown
that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo.
CONCLUSIONS: We have shown that SWI/SNF can modulate alternative pre-mRNA
processing, not only in cultured cells but also in vivo. The effect is restricted
to and specific for a subset of transcripts. Our results provide novel insights
into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic
diversity in higher eukaryotes.
PMID- 22047076
TI - Development of methods for studying the differentiation of human mesenchymal stem
cells under cyclic compressive strain.
AB - Human mesenchymal stem cells (hMSC) have numerous potential advantages over
terminally differentiated cells and embryonic stem cells for use in tissue
engineering applications. The aims of this study were to develop methods to test
the hypothesis that hMSC could be differentiated using cyclic compressive strain
alone. hMSC were successfully isolated, purified using D7-FIB antibody, cloned,
and characterized. The cells were subsequently analyzed using fluorescence
activated cell sorting using a panel of antibodies and differentiation into
multiple cell lineages. D7FIB-positive cells were then seeded into collagen
alginate scaffolds and subjected to 10% or 15% cyclic compressive strain for 4
out of 24 hours for up to 21 days in a bespoke servo-assisted displacement
controlled device. Cells were analyzed using adenosine triphosphate assay to
determine cell number, live-dead cell assay, and quantitative real-time
polymerase chain reaction at 7 and 21 days. Cloned D7-FIB-positive hMSCs showed
evidence of differentiation to an osteogenic lineage under 10% cyclic compressive
strain alone (core binding factor alpha 1 (CBFA-1) was significantly upregulated
at 7 and 21 days by a factor of 18.3 and 32.2, respectively) and to an osteo
chondrogenic lineage under 15% cyclic compressive strain alone (increased
expression of CBFA-1, Sox9, and aggrecan). A combination of a composite
viscoelastic scaffold and controlled cyclic compressive strain may be useful for
study of the differentiation of MSC.
PMID- 22047077
TI - Targeting the assembly of bacterial cell division protein FtsZ with small
molecules.
AB - FtsZ is the key protein of bacterial cell division and an emergent target for new
antibiotics. It is a filament-forming GTPase and a structural homologue of
eukaryotic tubulin. A number of FtsZ-interacting compounds have been reported,
some of which have powerful antibacterial activity. Here we review recent
advances and new approaches in modulating FtsZ assembly with small molecules.
This includes analyzing their chemical features, binding sites, mechanisms of
action, the methods employed, and computational insights, aimed at a better
understanding of their molecular recognition by FtsZ and at rational antibiotic
design.
PMID- 22047079
TI - A comparative analysis of MC4R gene sequence, polymorphism, and chromosomal
localization in Chinese raccoon dog and Arctic fox.
AB - Numerous mutations of the human melanocortin receptor type 4 (MC4R) gene are
responsible for monogenic obesity, and some of them appear to be associated with
predisposition or resistance to polygenic obesity. Thus, this gene is considered
a functional candidate for fat tissue accumulation and body weight in domestic
mammals. The aim of the study was comparative analysis of chromosome
localization, nucleotide sequence, and polymorphism of the MC4R gene in two
farmed species of the Canidae family, namely the Chinese raccoon dog (Nycterutes
procyonoides procyonoides) and the arctic fox (Alopex lagopus). The whole coding
sequence, including fragments of 3'UTR and 5'UTR, shows 89% similarity between
the arctic fox (1276 bp) and Chinese raccoon dog (1213 bp). Altogether, 30 farmed
Chinese raccoon dogs and 30 farmed arctic foxes were searched for polymorphisms.
In the Chinese raccoon dog, only one silent substitution in the coding sequence
was identified; whereas in the arctic fox, four InDels and two single-nucleotide
polymorphisms (SNPs) in the 5'UTR and six silent SNPs in the exon were found. The
studied gene was mapped by FISH to the Chinese raccoon dog chromosome 9
(NPP9q1.2) and arctic fox chromosome 24 (ALA24q1.2-1.3). The obtained results are
discussed in terms of genome evolution of species belonging to the family Canidae
and their potential use in animal breeding.
PMID- 22047078
TI - Structural and evolutionary divergence of eukaryotic protein kinases in
Apicomplexa.
AB - BACKGROUND: The Apicomplexa constitute an evolutionarily divergent phylum of
protozoan pathogens responsible for widespread parasitic diseases such as malaria
and toxoplasmosis. Many cellular functions in these medically important organisms
are controlled by protein kinases, which have emerged as promising drug targets
for parasitic diseases. However, an incomplete understanding of how apicomplexan
kinases structurally and mechanistically differ from their host counterparts has
hindered drug development efforts to target parasite kinases. RESULTS: We used
the wealth of sequence data recently made available for 15 apicomplexan species
to identify the kinome of each species and quantify the evolutionary constraints
imposed on each family of apicomplexan kinases. Our analysis revealed lineage
specific adaptations in selected families, namely cyclin-dependent kinase (CDK),
calcium-dependent protein kinase (CDPK) and CLK/LAMMER, which have been
identified as important in the pathogenesis of these organisms. Bayesian analysis
of selective constraints imposed on these families identified the sequence and
structural features that most distinguish apicomplexan protein kinases from their
homologs in model organisms and other eukaryotes. In particular, in a subfamily
of CDKs orthologous to Plasmodium falciparum crk-5, the activation loop contains
a novel PTxC motif which is absent from all CDKs outside Apicomplexa. Our
analysis also suggests a convergent mode of regulation in a subset of
apicomplexan CDPKs and mammalian MAPKs involving a commonly conserved arginine in
the alphaC helix. In all recognized apicomplexan CLKs, we find a set of co
conserved residues involved in substrate recognition and docking that are
distinct from metazoan CLKs. CONCLUSIONS: We pinpoint key conserved residues that
can be predicted to mediate functional differences from eukaryotic homologs in
three identified kinase families. We discuss the structural, functional and
evolutionary implications of these lineage-specific variations and propose
specific hypotheses for experimental investigation. The apicomplexan-specific
kinase features reported in this study can be used in the design of selective
kinase inhibitors.
PMID- 22047080
TI - MMP7 -181G allele is a low-penetrant risk factor for cancer development in East
Asians.
AB - Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with
broad substrate specificity. Its expression is associated with tumor invasion,
metastasis, and survival for a number of cancers. However, data from published
studies with individually low statistical power are conflicting. Here, we
performed a meta-analysis of 14 publications (16 case-control studies) to better
assess the purported relationship. Eligible studies were identified by searching
the Pubmed database. Odds ratios (ORs) with 95% confidence intervals (CIs) were
estimated to assess the association. Overall, we found that the -181 G allele
increased cancer risk in East Asians (G-allele vs. A-allele, OR=1.35, 95% CI:
1.25-1.46, P(heterogeneity)=0.01; GA vs. AA, OR=1.40, 95% CI: 1.16-1.69,
P(heterogeneity)=0.04; GG+GA vs. AA, OR=1.52, 95% CI: 1.30-1.78,
P(heterogeneity)=0.00). Similarly, in the stratified analysis by cancer type and
source of control, significantly increased cancer risk was indicated. Our study
showed evidence that MMP7 -181A/G polymorphism may increase cancer risk in the
East Asian population. Future studies with larger sample size are warranted to
further evaluate this association in greater detail.
PMID- 22047081
TI - Analysis of p53 tumor suppressor pathway genes in chronic lymphocytic leukemia.
AB - The p53 tumor suppressor gene plays an important role in preventing tumor
development. The p53 protein interacts with other p53 signal pathway members to
control cell proliferation. In this study, expression of the p53, Human homolog
of murine Double Minute 2 (HDM2), p14Alternating Reading Frame (ARF), Zinc Finger
and BTB domain containing 7A (ZBTB7A), and B-Cell Lymphoma 6 (BCL6) genes was
quantitatively investigated by real-time polymerase chain reaction (PCR) in the
peripheral blood of patients with chronic lymphocytic leukemia (CLL) and healthy
controls. Plasma fibronectin levels were determined by enzyme-linked
immunosorbent assay. Expression of the p53, p14, and HDM2 genes were
significantly higher in the patients. However, ZBTB7A and BCL6 gene expression
was not detectable in both groups. A positive correlation between p14ARF and HDM2
expression and a negative correlation between p53 and p14ARF expression was
observed. Expression of the p14ARF and HDM2 genes were inversely correlated in
the control group. Neither HDM2 nor p14ARF gene expression was correlated with
p53 expression. The p53 gene was also analyzed for the presence of mutations. A
splice-site mutation was found in a single patient. Our findings indicate that
expression of the p53, p14ARF, and HDM2 genes are associated with CLL.
Elucidation of the mutual interactions at the protein level warrants further
studies.
PMID- 22047083
TI - Regioselective synthesis and slow-release Suzuki-Miyaura cross-coupling of MIDA
boronate-functionalized isoxazoles and triazoles.
AB - The efficient preparation of heterocycles with a range of substitutions ortho to
heteroatoms remains as a challenge in organic synthesis, particularly relevant to
the construction of druglike molecules due to the ubiquitous presence of such
moieties in that chemical space. Modular installation of heterocyclic building
blocks using Suzuki-Miyaura cross-coupling is a conceptually useful strategy to
address this challenge, though this has historically been met with technical
difficulty due to issues of inaccessibility and instability of the requisite
heterocyclic boronates. Herein we report a mild and highly regioselective
cycloaddition approach which affords convenient access to stable MIDA boronate
functionalized isoxazoles and triazoles and their subsequent efficient Suzuki
Miyaura cross-coupling. This methodology is then further applied to a set of
druglike compounds in an efficient one-pot telescoped sequence in line with green
chemistry principles.
PMID- 22047082
TI - EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 as potential prognostic markers for
postoperative Taiwanese colorectal cancer patients.
AB - Undetected micrometastasis may play a key role in the early relapse of colorectal
cancer (CRC) patients. The aim of this study was to detect circulating tumor
cells (CTCs) for predicting early relapse of CRC patients by a weighted enzymatic
chip array (WEnCA) and analyze 15 candidate genes associated with CRC
carcinogenesis. The genes of 105 postoperative CRC patients were analyzed by
membrane array and direct sequencing. We constructed a WEnCA platform including
five prognosis-related genes and analyzed the detection rate of WEnCA for CTCs in
30 clinically confirmed CRC relapse patients. Postoperative relapse was
significantly correlated with gene overexpression, including EVI2B (p=0.001,
OR=4.622), ATP2A2 (p=0.006, OR=4.688), S100B (p=0.001, OR=11.521), TM4SF3
(p=0.001, OR=6.756), and OLFM4 (p=0.008, OR=3.545). Using WEnCA (weighting score
of each gene: 5 to EVI2B, 5 to ATP2A2, 12 to S100B, 7 to TM4SF3, and 4 to OLFM4),
we could detect CTCs presenting these genotypes in relapsed CRC patients. The
sensitivity, specificity, and accuracy were 94.7%, 93.5%, and 97%, respectively.
The results of the present study suggest that EVI2B, ATP2A2, S100B, TM4SF3, and
OLFM4 could be potential prognostic markers for CRC patients.
PMID- 22047084
TI - Generation of recombinant single-chain antibodies neutralizing the cytolytic
activity of vaginolysin, the main virulence factor of Gardnerella vaginalis.
AB - BACKGROUND: Gardnerella vaginalis is identified as the predominant colonist of
the vaginal tract in women with bacterial vaginosis. Vaginolysin (VLY) is a
protein toxin released by G. vaginalis. VLY possesses cytolytic activity and is
considered as a main virulence factor of G. vaginalis. Inhibition of VLY-mediated
cell lysis by antibodies may have important physiological relevance. RESULTS:
Single-chain variable fragments of immunoglobulins (scFvs) were cloned from two
hybridoma cell lines producing neutralizing antibodies against VLY and expressed
as active proteins in E. coli. For each hybridoma, two variants of anti-VLY scFv
consisting of either VL-VH or VH-VL linked with a 20 aa-long linker sequence
(G4S)4 were constructed. Recovery of scFvs from inclusion bodies with subsequent
purification by metal-chelate chromatography resulted in VLY-binding proteins
that were predominantly monomeric. The antigen-binding activity of purified scFvs
was verified by an indirect ELISA. The neutralizing activity was investigated by
in vitro hemolytic assay and cytolytic assay using HeLa cell line. Calculated
apparent Kd values and neutralizing potency of scFvs were in agreement with those
of parental full-length antibodies. VH-VL and VL-VH variants of scFvs showed
similar affinity and neutralizing potency. The anti-VLY scFvs derived from
hybridoma clone 9B4 exhibited high VLY-neutralizing activity both on human
erythrocytes and cervical epithelial HeLa cells. CONCLUSIONS: Hybridoma-derived
scFvs with VLY-binding activity were expressed in E. coli. Recombinant anti-VLY
scFvs inhibited VLY-mediated cell lysis. The monovalent scFvs showed reduced
affinity and neutralizing potency as compared to the respective full-length
antibodies. The loss of avidity could be restored by generating scFv constructs
with multivalent binding properties. Generated scFvs is the first example of
recombinant single-chain antibodies with VLY-neutralizing activity produced in
prokaryote expression system. G. vaginalis caused infections continue to be a
world-wide problem, therefore neutralizing recombinant antibodies may provide
novel therapeutic agents useful in the treatment of bacterial vaginosis and other
diseases caused by G. vaginalis.
PMID- 22047085
TI - Oxidative stress-induced modifications of histidyl-tRNA synthetase affect its
tRNA aminoacylation activity but not its immunoreactivity.
AB - The aminoacyl-tRNA synthetases are ubiquitously expressed enzymes that catalyze
the esterification of amino acids to their cognate tRNAs. Autoantibodies against
several aminoacyl-tRNA synthetases are found in autoimmune polymyositis and
dermatomyositis patients. Because necrosis is often found in skeletal muscle
biopsies of these patients, we hypothesized that cell-death-induced protein
modifications may help in breaking immunological tolerance. Since cell death is
associated with oxidative stress, the effect of oxidative stress on the main
myositis-specific autoantibody target Jo-1 (histidyl-tRNA synthetase; HisRS) was
studied in detail. The exposure of Jurkat cells to hydrogen peroxide resulted in
the detection of several oxidized methionines and one oxidized tryptophan residue
in the HisRS protein, as demonstrated by mass spectrometry. Unexpectedly, the
tRNA aminoacylation activity of HisRS appeared to be increased upon oxidative
modification. The analysis of myositis patient sera did not lead to the detection
of autoantibodies that are specifically reactive with the modified HisRS protein.
The results of this study demonstrate that the Jo-1/HisRS autoantigen is modified
under oxidative stress conditions. The consequences of these modifications for
the function of HisRS and its autoantigenicity are discussed.
PMID- 22047087
TI - IVth International Symposium of Veterinary Laboratory Diagnosticians (report).
PMID- 22047086
TI - A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on
antiretroviral therapy.
AB - BACKGROUND: Trichomonas vaginalis has been associated with increased vaginal HIV
1 RNA shedding in antiretroviral therapy (ART)-naive women. The effect of
trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been
characterized. We tested the hypothesis that T. vaginalis infection would
increase vaginal HIV-1 RNA shedding in women on ART, and that successful
treatment would reduce vaginal HIV-1 RNA levels. METHODS: We conducted a
prospective cohort study including monthly follow-up of 147 women receiving ART
in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of
motile trichomonads on vaginal saline wet mount, received treatment with single
dose metronidazole (2 g). Test of cure was performed at the next monthly visit.
Using the pre-infection visit as the reference category, we compared detection of
vaginal HIV-1 RNA before versus during and after infection using generalized
estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the
lower limit for linear quantitation. RESULTS: Among 31 women treated for
trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for
quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI
4% - 30%]), 4 (13% [95% CI 4% - 30%]), and 5 (16% [95% confidence interval {CI}
5% - 34%]) women respectively. After adjusting for potential confounding factors,
we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA
before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p =
0.7). In addition, detection of HIV-1 RNA was similar before infection versus
after successful treatment (OR 0.68, 95% CI (0.13 - 3.45), p = 0.6). CONCLUSION:
Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during
and after T. vaginalis infection.
PMID- 22047089
TI - Assessment of the knowledge of graphical symbols labelled on malaria rapid
diagnostic tests in four international settings.
AB - BACKGROUND: Graphical symbols on in vitro diagnostics (IVD symbols) replace the
need for text in different languages and are used on malaria rapid diagnostic
tests (RDTs) marketed worldwide. The present study assessed the comprehension of
IVD symbols labelled on malaria RDT kits among laboratory staff in four different
countries. METHODS: Participants (n = 293) in Belgium (n = 96), the Democratic
Republic of the Congo (DRC, n = 87), Cambodia (n = 59) and Cuba (n = 51) were
presented with an anonymous questionnaire with IVD symbols extracted from ISO
15223 and EN 980 presented as stand-alone symbols (n = 18) and in context
(affixed on RDT packages, n = 16). Responses were open-ended and scored for
correctness by local professionals. RESULTS: Presented as stand-alone, three and
five IVD symbols were correctly scored for comprehension by 67% and 50% of
participants; when contextually presented, five and seven symbols reached the 67%
and 50% correct score respectively. 'Batch code' scored best (correctly scored by
71.3% of participants when presented as stand-alone), 'Authorized representative
in the European Community' scored worst (1.4% correct). Another six IVD symbols
were scored correctly by less than 10% of participants: 'Do not reuse', 'In vitro
diagnostic medical device', 'Sufficient for', 'Date of manufacture', 'Authorised
representative in EC', and 'Do not use if package is damaged'. Participants in
Belgium and Cuba both scored six symbols above the 67% criterion, participants
from DRC and Cambodia scored only two and one symbols above this criterion. Low
correct scores were observed for safety-related IVD symbols, such as for
'Biological Risk' (42.7%) and 'Do not reuse' (10.9%). CONCLUSION: Comprehension
of IVD symbols on RDTs among laboratory staff in four international settings was
unsatisfactory. Administrative and outreach procedures should be undertaken to
assure their acquaintance by end-users.
PMID- 22047092
TI - Reply to "Comment on 'Electronic structures, vibrational and thermochemical
properties of neutral and charged niobium clusters Nb(n), n = 7-12'".
PMID- 22047090
TI - Novel pharmacotherapeutic treatments for cocaine addiction.
AB - Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and
serotonin in the brain due to prevention of their re-uptake into the neuron that
released the neurotransmitter. Cocaine dependence is a public health concern and
cause of significant morbidity and mortality worldwide. At present, there are no
approved medications for the treatment of this devastating illness, and
behavioral interventions have proven to be of limited use. However, there have
been a number of recent trials testing promising agents including dopamine
agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most
recent human clinical trials of potential medications for treatment of cocaine
dependence, as well as pre-clinical studies for another promising agent, levo
tetrahydropalmatine. Examination of these recent findings shows promise for
GABAergic medications and the cocaine vaccine, as well as unique medications such
as disulfiram, whose mechanism remains to be determined. Future work may also
confirm specific subgroups of patients for treatment response based on clinical
characteristics, biomarkers and pharmacogenetics. This review highlights the need
for further, bigger studies in order to determine optimal clinical usage.
PMID- 22047093
TI - The impact of recombinant fusion-hydrophobin coated surfaces on E. coli and
natural mixed culture biofilm formation.
AB - The impact of increased surface hydrophobicity on biofilms regarding retardation,
repulsion, or attraction was studied with hydrophobin modified glass substrata.
Recombinantly produced fungal hydrophobins forming self-assembled monolayers were
used as the surface coating. The adsorption dynamics of hydrophobins were
analysed with a quartz crystal microbalance which showed the surface coating to
be rapid and stable. The change of surface wettability was determined by water
contact angle measurements and demonstrated an increase in hydrophobicity in
range of 60-62 degrees . The homogeneity of the monolayers was demonstrated by
immunofluorescence microscopy. Atomic force microscopy was applied to visualise
the uniform texture of the coated materials. The hydrophobin coatings had no
impact on different biofilms in terms of spatial distribution, cell numbers, and
population composition. In consequence, hydrophobicity might not represent an
important parameter for biofilm formation. Nevertheless, recombinant hydrophobins
are suitable for large scale surface modification and functionalization with
bioactive molecules.
PMID- 22047094
TI - A new strategy to investigate the toxicity of nanomaterials using Langmuir
monolayers as membrane models.
AB - Nanomaterials such as carbon nanotubes (CNTs) and nanoparticles have received
enormous attention in analytical areas for their potential applications as new
tools for biotechnology and life sciences. Most of these possible applications
involve the use of CNTs and related materials as vehicles for drug delivery
and/or gene therapy. In this study, we introduce a methodology to evaluate the
interactions between CNTs/dendrimers nanoconjugates and phospholipid biomembrane
models, using the Langmuir film balance technique. Our main goal was to elucidate
the action of engineered nanomaterials in cell membranes, at the molecular level,
using a membrane model system. The penetration of single-walled carbon nanotubes
(SWCNTs)/polyamidoamine dendrimer nanocomplexes into
dipalmitoylphosphatidylcholine monolayers was pronounced, as revealed by
adsorption kinetics and surface pressure measurements. These findings suggest
that SWCNTs were able to interact even at high surface pressure values, ~30 mN/m.
Therefore, the results confirm that the presence of the nanomaterial affects the
packing of the synthetic membranes. We believe the methodology introduced here
may be of great importance for further nanotoxicity studies.
PMID- 22047095
TI - Droplet size scaling of water-in-oil emulsions under turbulent flow.
AB - The size of droplets in emulsions is important in many industrial, biological,
and environmental systems, as it determines the stability, rheology, and area
available in the emulsion for physical or chemical processes that occur at the
interface. While the balance of fluid inertia and surface tension in determining
droplet size under turbulent mixing in the inertial subrange has been well
established, the classical scaling prediction by Shinnar half a century ago of
the dependence of droplet size on the viscosity of the continuous phase in the
viscous subrange has not been clearly validated in experiment. By employing
extremely stable suspensions of highly viscous oils as the continuous phase and
using a particle video microscope (PVM) probe and a focused beam reflectance
method (FBRM) probe, we report measurements spanning 2 orders of magnitude in the
continuous phase viscosity for the size of droplets in water-in-oil emulsions.
The wide range in measurements allowed identification of a scaling regime of
droplet size proportional to the inverse square root of the viscosity, consistent
with the viscous subrange theory of Shinnar. A single curve for droplet size
based on the Reynolds and Weber numbers is shown to accurately predict droplet
size for a range of shear rates, mixing geometries, interfacial tensions, and
viscosities. Viscous subrange control of droplet size is shown to be important
for high viscous shear stresses, i.e., very high shear rates, as is desirable or
found in many industrial or natural processes, or very high viscosities, as is
the case in the present study.
PMID- 22047096
TI - Efficient generation of ortho-quinone methide: application to the biomimetic
syntheses of (+/-)-schefflone and tocopherol trimers.
AB - An efficient method using silver oxide-mediated oxidation for the synthesis of
ortho-quinone methides has been developed and applied to the biomimetic syntheses
of novel trimeric natural products, (+/-)-schefflone and tocopherol trimers.
Further studies of the critical trimerization as well as substrate scope and
limitations are also reported.
PMID- 22047097
TI - Trends in health-related behavioral risk factors among pregnant women in the
United States: 2001-2009.
AB - BACKGROUND: Unhealthy lifestyle behaviors during pregnancy often predispose women
to multiple risks including adverse pregnancy outcomes and impaired health status
for mothers. This study assessed the trends in the prevalence of health-related
behavioral risk factors over time among U.S. pregnant women. METHODS: Data from
22,604 pregnant women aged 18-44 years who participated in the 2001-2009
Behavioral Risk Factor Surveillance System were analyzed to assess the trends in
the prevalence of behavioral risk factors. Correlates of having individual or
clustering healthy behaviors were also assessed among 2295 pregnant women in the
2009 survey. RESULTS: From 2001 to 2009, among pregnant women, the age-adjusted
prevalence of engaging in leisure-time exercise and receiving influenza
vaccination increased significantly (p<0.05 for linear trends); the prevalence of
any alcohol consumption decreased marginally (p=0.065 for linear trend); and the
prevalence of binge drinking, smoking, and consuming fruits and vegetables >=5
times/day varied little. Over the 9 years, the percentages of pregnant women who
reported having all four healthy behaviors (i.e., not currently smoking, no
alcohol consumption, engaging in leisure-time exercise, and receiving influenza
vaccination) increased linearly from 7.3% in 2001 to 21.2% in 2009 (p<0.001).
Sociodemographic characteristics, perceived health status, and health-care
availability were differentially associated with certain individual or clustered
healthy behaviors. CONCLUSIONS: Increased efforts emphasizing multiple health
related behavioral risk factors including reducing alcohol use, binge drinking,
and smoking and improving fruit and vegetable consumption during pregnancy are
needed.
PMID- 22047098
TI - Obstetric and perinatal outcomes in women with eating disorders.
AB - BACKGROUND: We wished to investigate whether women with a history of eating
disorders have an increased risk for adverse obstetric and perinatal outcomes.
STUDY DESIGN: A retrospective study was conducted comparing pregnancy
complications in patients with and without eating disorders. Deliveries occurred
during the years 1988-2009 in a tertiary medical center. Women lacking prenatal
care and with multiple gestations were excluded from the study. Stratified
analyses were performed using multivariable logistic regression models. Odds
ratios (OR) and their 95% confidence interval (CI) were computed. A p value<0.05
was considered statistically significant. RESULTS: During the study period, of
117,875 singleton deliveries, 122 (0.1%) occurred in patients with eating
disorders. Eating disorders were significantly associated with fertility
treatments (5.7% vs. 2.8%, p=0.047), intrauterine growth restriction (7.4% vs.
2.3%, p<0.001), term low birth weight (<2500 g) (7.4% vs. 2.8%, p=0.002), preterm
delivery (15.6% vs. 7.5%, p=0.002), and cesarean delivery (25.4% vs. 15.0%,
p=0.001). Using multivariable analyses, low birth weight (OR 2.5, 95% CI 1.3
5.0), preterm delivery (OR 2.2, 95% CI 1.4-3.6), and cesarean section (OR 1.9,
95% CI 1.3-2.9) were significantly associated with eating disorders. CONCLUSIONS:
Eating disorders are associated with increased risk of adverse pregnancy
outcomes. Accordingly, careful surveillance is needed for early detection of
possible complications.
PMID- 22047099
TI - Perimenopausal vaginal bleeding: diagnostic evaluation and therapeutic options.
AB - While significant awareness has been raised about menopause, less attention has
been focused on the perimenopausal or "menopausal transition" period. Many women
and their physicians remain unaware of the impact of this transitional phase into
menopause. Specifically, heavy and unpredictable perimenopausal bleeding is
extremely common. It is a normal phenomenon of aging and tends to improve over
time. However, about one quarter of perimenopausal women will have heavy flow
that persists beyond 3 months and will require medical assistance. The purpose of
this review is to focus on the hormonal and physiologic changes that are
associated with perimenopausal heavy vaginal bleeding, to present the essential
evaluation of causes for this heavy flow, and to outline the evidence for
effective medical and surgical treatments. Advances in the understanding of the
normal physiology of perimenopause have led to medical therapies that may lead to
fewer surgical procedures and hysterectomies and should be of interest to health
care practitioners focusing on women's health. Although these issues are
addressed in the gynecologic literature, there is relatively less published in
other disciplines.
PMID- 22047100
TI - Contrasting effects of errorless naming treatment and gestural facilitation for
word retrieval in aphasia.
AB - We compared the effects of two treatments for aphasic word retrieval impairments,
errorless naming treatment (ENT) and gestural facilitation of naming (GES),
within the same individuals, anticipating that the use of gesture would enhance
the effect of treatment over errorless treatment alone. In addition to picture
naming, we evaluated results for other outcome measures that were largely
untested in earlier ENT studies. In a single participant crossover treatment
design, we examined the effects of ENT and GES in eight individuals with stroke
induced aphasia and word retrieval impairments (three semantic anomia, five
phonological anomia) in counterbalanced phases across participants. We evaluated
effects of the two treatments for a daily picture naming/gesture production probe
measure and in standardised aphasia tests and communication rating scales
administered across phases of the experiment. Both treatments led to
improvements in naming of trained words (small-to-large effect sizes) in
individuals with semantic and phonological anomia. Small generalised naming
improvements were noted for three individuals with phonological anomia. GES
improved use of corresponding gestures for trained words (large effect sizes).
Results were largely maintained at one month post-treatment completion. Increases
in scores on standardised aphasia testing also occurred for both ENT and GES
training. Both ENT and GES led to improvements in naming measures, with no
clear difference between treatments. Increased use of gestures following GES
provided a potential compensatory means of communication for those who did not
improve verbal skills. Both treatments are considered to be effective methods to
promote recovery of word retrieval and verbal production skills in individuals
with aphasia.
PMID- 22047101
TI - Simultaneous determination of mono-, di-, and triglycerides in multiphase systems
by online Fourier transform infrared spectroscopy.
AB - Glycerides are of significant value for industry as ingredients with different
purposes in food or cosmetics. The analysis of glycerides is mainly performed by
gas chromatography (GC) or high-pressure liquid chromatography (HPLC), which
demonstrate limitations in dealing with multiphase systems. In this article, an
in situ differentiation between mono-, di-, and triglycerides in multiphase
systems by Fourier transform infrared (FT-IR) spectroscopy is demonstrated. The
enzymatic esterification of glycerol with lauric acid was analyzed as a model
system. The reaction was carried out in a bubble column reactor containing four
phases (two liquid phases of glycerol and lauric acid, air as gaseous phase, and
a heterogeneous catalyst as solid phase). As a feasibility study, a chemometric
model was generated for the pure components only. The quantities of lauric acid
and the three products (mono-, di-, and trilaurin) were simultaneously determined
over the course of the reaction with acceptable errors (1.8-12.5%) with regard to
the calibration effort. This technology has the potential to give accurate
results, particularly in unstable emulsion systems containing fats, oils, or
emulsifiers, which are currently afflicted by analytical errors caused by the
challenge of accurate sampling.
PMID- 22047102
TI - Rapid eye movements during sleep in mice: high trait-like stability qualifies
rapid eye movement density for characterization of phenotypic variation in sleep
patterns of rodents.
AB - BACKGROUND: In humans, rapid eye movements (REM) density during REM sleep plays a
prominent role in psychiatric diseases. Especially in depression, an increased
REM density is a vulnerability marker for depression. In clinical practice and
research measurement of REM density is highly standardized. In basic animal
research, almost no tools are available to obtain and systematically evaluate eye
movement data, although, this would create increased comparability between human
and animal sleep studies. METHODS: We obtained standardized
electroencephalographic (EEG), electromyographic (EMG) and electrooculographic
(EOG) signals from freely behaving mice. EOG electrodes were bilaterally and
chronically implanted with placement of the electrodes directly between the
musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG
and EOG signals were obtained for four days. Subsequent to the implantation
process, we developed and validated an Eye Movement scoring in Mice Algorithm
(EMMA) to detect REM as singularities of the EOG signal, based on wavelet
methodology. RESULTS: The distribution of wakefulness, non-REM (NREM) sleep and
rapid eye movement (REM) sleep was typical of nocturnal rodents with small
amounts of wakefulness and large amounts of NREM sleep during the light period
and reversed proportions during the dark period. REM sleep was distributed
correspondingly. REM density was significantly higher during REM sleep than NREM
sleep. REM bursts were detected more often at the end of the dark period than the
beginning of the light period. During REM sleep REM density showed an ultradian
course, and during NREM sleep REM density peaked at the beginning of the dark
period. Concerning individual eye movements, REM duration was longer and
amplitude was lower during REM sleep than NREM sleep. The majority of single REM
and REM bursts were associated with micro-arousals during NREM sleep, but not
during REM sleep. CONCLUSIONS: Sleep-stage specific distributions of REM in mice
correspond to human REM density during sleep. REM density, now also assessable in
animal models through our approach, is increased in humans after acute stress,
during PTSD and in depression. This relationship can now be exploited to match
animal models more closely to clinical situations, especially in animal models of
depression.
PMID- 22047103
TI - 3,4-dihydroxyphenylalanine-assisted hydroxyapatite nanoparticle coating on
polymer scaffolds for efficient osteoconduction.
AB - For bone regeneration applications, scaffolds made from a composite of a
biodegradable polymer and ceramic have advantages over scaffolds made from only
one component (biodegradable polymer or ceramic alone). In this study, a simple
and rapid method was developed to induce hydroxyapatite (HA) nanoparticle
adsorption on polyglycolic acid (PGA) scaffold surfaces. PGA meshes were coated
with HA nanoparticles by immersing the scaffolds in a buffer solution containing
3,4-dihydroxyphenylalanine (DOPA), a critical, functional element in mussel
adhesive protein known to strongly bind to various materials. Substantial HA
coating on PGA scaffolds was achieved within 24 hours of immersion, as determined
according to selective staining of ceramic particles, scanning electron
microscopy, X-ray photoelectron spectroscopy, and energy-dispersive spectroscopy.
To evaluate the osteoconduction efficacy of the scaffolds in vivo, PGA scaffolds,
DOPA-coated PGA scaffolds, PGA scaffolds immersed in HA solution, and HA- and
DOPA-coated PGA (HA-DOPA-PGA) scaffolds were implanted in critical-sized defects
in mouse skulls for 8 weeks. Micro-computed tomography and histological analyses
showed that bone regeneration in vivo was far more extensive on HA-DOPA-PGA
scaffolds than on the other scaffolds. DOPA offers an efficient and simple method
of HA coating on polymer scaffolds. HA-polymer composite scaffolds fabricated
using this method could be useful as bone graft.
PMID- 22047104
TI - Binding of 3,4,5,6-tetrahydroxyazepanes to the acid-beta-glucosidase active site:
implications for pharmacological chaperone design for Gaucher disease.
AB - Pharmacologic chaperoning is a therapeutic strategy being developed to improve
the cellular folding and trafficking defects associated with Gaucher disease, a
lysosomal storage disorder caused by point mutations in the gene encoding acid
beta-glucosidase (GCase). In this approach, small molecules bind to and stabilize
mutant folded or nearly folded GCase in the endoplasmic reticulum (ER),
increasing the concentration of folded, functional GCase trafficked to the
lysosome where the mutant enzyme can hydrolyze the accumulated substrate. To
date, the pharmacologic chaperone (PC) candidates that have been investigated
largely have been active site-directed inhibitors of GCase, usually containing
five- or six-membered rings, such as modified azasugars. Here we show that a
seven-membered, nitrogen-containing heterocycle (3,4,5,6-tetrahydroxyazepane)
scaffold is also promising for generating PCs for GCase. Crystal structures
reveal that the core azepane stabilizes GCase in a variation of its proposed
active conformation, whereas binding of an analogue with an N-linked hydroxyethyl
tail stabilizes GCase in a conformation in which the active site is covered, also
utilizing a loop conformation not seen previously. Although both compounds
preferentially stabilize GCase to thermal denaturation at pH 7.4, reflective of
the pH in the ER, only the core azepane, which is a mid-micromolar competitive
inhibitor, elicits a modest increase in enzyme activity for the neuronopathic
G202R and the non-neuronopathic N370S mutant GCase in an intact cell assay. Our
results emphasize the importance of the conformational variability of the GCase
active site in the design of competitive inhibitors as PCs for Gaucher disease.
PMID- 22047106
TI - Engineering an L-cell line that expresses insulin under the control of the
glucagon-like peptide-1 promoter for diabetes treatment.
AB - BACKGROUND: Diabetes mellitus is a complicated disease with a pathophysiology
that includes hyperinsulinemia, hyperglycemia and other metabolic impairments
leading to many clinical complications. It is necessary to develop appropriate
treatments to manage the disease and reduce possible acute and chronic side
effects. The advent of gene therapy has generated excitement in the medical world
for the possible application of gene therapy in the treatment of diabetes. The
glucagon-like peptide-1 (GLP-1) promoter, which is recognised by gut L-cells, is
an appealing candidate for gene therapy purposes. The specific properties of L
cells suggest that L-cells and the GLP-1 promoter would be useful for diabetes
therapy approaches. RESULTS: In this study, L-cells were isolated from a primary
intestinal cell line to create suitable target cells for insulin expression
studies. The isolated cells displayed L-cell properties and were therefore used
as an L-cell surrogate. Next, the isolated L-cells were transfected with the
recombinant plasmid consisting of an insulin gene located downstream of the GLP-1
promoter. The secretion tests revealed that an increase in glucose concentration
from 5 mM to 25 mM induced insulin gene expression in the L-cells by 2.7-fold.
Furthermore, L-cells quickly responded to the glucose stimulation; the amount of
insulin protein increased 2-fold in the first 30 minutes and then reached a
plateau after 90 minutes. CONCLUSION: Our data showed that L-cells efficiently
produced the mature insulin protein. In addition, the insulin protein secretion
was positively regulated with glucose induction. In conclusion, GLP-1 promoter
and L-cell could be potential candidates for diabetes gene therapy agents.
PMID- 22047105
TI - Spinal muscular atrophy.
AB - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease
characterized by degeneration of alpha motor neurons in the spinal cord,
resulting in progressive proximal muscle weakness and paralysis. Estimated
incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40
1/60. This disease is characterized by generalized muscle weakness and atrophy
predominating in proximal limb muscles, and phenotype is classified into four
grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor
function achieved. This disease is caused by homozygous mutations of the survival
motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients
the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1
exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity.
Differential diagnosis should be considered with other neuromuscular disorders
which are not associated with increased CK manifesting as infantile hypotonia or
as limb girdle weakness starting later in life. Considering the high carrier
frequency, carrier testing is requested by siblings of patients or of parents of
SMA children and are aimed at gaining information that may help with reproductive
planning. Individuals at risk should be tested first and, in case of testing
positive, the partner should be then analyzed. It is recommended that in case of
a request on carrier testing on siblings of an affected SMA infant, a detailed
neurological examination should be done and consideration given doing the direct
test to exclude SMA. Prenatal diagnosis should be offered to couples who have
previously had a child affected with SMA (recurrence risk 25%). The role of
follow-up coordination has to be managed by an expert in neuromuscular disorders
and in SMA who is able to plan a multidisciplinary intervention that includes
pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on
the phenotypic severity going from high mortality within the first year for SMA
type 1 to no mortality for the chronic and later onset forms.
PMID- 22047107
TI - Development of a peptide-targeted, myocardial ischemia-homing, mesenchymal stem
cell.
AB - Directing stem cells to the heart is critical in producing an effective cell
therapy for myocardial infarction (MI). Mesenchymal stem cells (MSCs) offer an
exquisite drug delivery platform with environment-sensing cytokine release and
MSCs have shown therapeutic potential in MI. Peptide-based targeting offers a
novel method to increase cell homing, wherein MI-specific peptides, identified by
phage display, are synthesized with a palmitic acid tail to facilitate cell
membrane integration. Phage-peptides were screened in a mouse MI model and four
peptides (CRPPR, CRKDKC, KSTRKS, and CARSKNKDC) were selected and synthesized as
palmitated derivatives for further investigation. Cell coating was optimized and
coating persistence and cytotoxicity were evaluated. MSCs were coated with
peptides, injected into mice with MI, and MSCs in the heart quantified. Greater
numbers of MSCs were found in heart of animals treated with the peptide-coated
MSCs compared to uncoated controls. MSC numbers had positive correlation with MI
severity in peptide-coated cells but a negative correlation in MSCs alone. A
transient cell coating ("painting") method has been developed that labels cells
efficiently, non-toxically and increases cell localization in MI hearts.
PMID- 22047108
TI - Quantum-chemical insights into the prediction of charge transport parameters for
a naphthalenetetracarboxydiimide-based copolymer with enhanced electron mobility.
AB - Theoretical modeling has been applied to study the charge transport (CT)
parameters of a high-electron-mobility (n-type) naphthalenetetracarboxydiimide
copolymer that was recently synthesized and tested for organic field-effect
transistor applications. To understand the physicochemical characteristics of
such a material, the intra- and intermolecular CT properties of holes and
electrons were investigated using different DFT functionals, evidencing the need
of range-separated hybrid functionals to predict key parameters such as the hole
and electron reorganization energies. Our calculations revealed clear differences
between hole- and electron-charging processes, providing fundamental elements for
the rationalization of their transport.
PMID- 22047109
TI - Effect of freezing time on macronutrients and energy content of breastmilk.
AB - BACKGROUND: In neonatal units and human milk banks freezing breastmilk at less
than -20 degrees C is the choice for preserving it. Scientific evidence in
relation to the loss of nutritional quality during freezing is rare. Our main aim
in this study is to determine the effect of freezing time up to 3 months on the
content of fat, total nitrogen, lactose, and energy. Our secondary aim is to
assess whether ultrasonic homogenization of samples enables a more suitable
reading of breastmilk macronutrients with a human milk analyzer (HMA) (MIRIS,
Uppsala, Sweden). METHODS: Refrigerated breastmilk samples were collected. Each
sample was divided into six pairs of aliquots. One pair was analyzed on day 0,
and the remaining pairs were frozen and analyzed, one each at 7, 15, 30, 60, and
90 days later. For each pair, one aliquot was homogenized by stirring, and the
other by applying ultrasound. Samples were analyzed with the HMA. RESULTS: By 3
months from freezing with the two homogenization methods, we observed a relevant
and significant decline in the concentration of fat and energy content. The
modification of total nitrogen and lactose was not constant and of lower
magnitude. The absolute concentration of all macronutrients and calories was
greater with ultrasonic homogenization. CONCLUSIONS: After 3 months from freezing
at -20 degrees C, an important decrease in fat and caloric content is observed.
Correct homogenization is fundamental for correct nutritional analysis.
PMID- 22047110
TI - Effect of Fluid Supplementation on Serum Bilirubin Level During Phototherapy of
Exclusively Breastfed Term Infants with Hyperbilirubinemia.
AB - Abstract Background: This study compared the rates of decrease in serum
bilirubin levels in severely jaundiced healthy term infants given oral or
intravenous fluid supplementation during phototherapy. Methods: A randomized
controlled study was carried out in the neonatal intensive care unit of Zeynep
Kamil Maternity and Children Hospital (Istanbul, Turkey) over a 4-month period.
Two hundred fifty healthy term infants with hyperbilirubinemia were randomized to
receive either solely breastmilk (n=125) or both breastmilk and intravenous fluid
(n=125) during phototherapy. Results: There were no significant differences
(p>0.05) in the mean birth weight, mean gestastional age, modes of delivery, mean
time of admission age, mean serum osmolality, and hematocrit and reticulocyte
count between the two groups. Similarly, there was no significant difference
(p>0.05) in the mean indirect serum bilirubin level at the time of admission to
the neonatal intensive care unit and at 4, 8, 12, 24, and 48 hours after
commencement of phototherapy between the two groups. There was no significant
difference (p>0.05) in the mean duration of phototherapy or in the median
duration of hospitalization between the two groups. Conclusions: Based on our
results, intravenous fluid support has no effect on the rate of decrease in serum
bilirubin and decrease in duration of phototherapy in healthy term newborns with
no dehydratation. However, using the oral route avoided the need for intravenous
cannulae and their attendant complications. Insensible fluid loss is increased
during phototherapy, so protection of hydration status with oral feeding is
important for newborns.
PMID- 22047111
TI - Molecular phylogeny of the higher and lower taxonomy of the Fusarium genus and
differences in the evolutionary histories of multiple genes.
AB - BACKGROUND: Species of the Fusarium genus are important fungi which is associated
with health hazards in human and animals. The taxonomy of this genus has been a
subject of controversy for many years. Although many researchers have applied
molecular phylogenetic analysis to examine the taxonomy of Fusarium species,
their phylogenetic relationships remain unclear only few comprehensive
phylogenetic analyses of the Fusarium genus and a lack of suitable nucleotides
and amino acid substitution rates. A previous stugy with whole genome comparison
among Fusairum species revealed the possibility that each gene in Fusarium
genomes has a unique evolutionary history, and such gene may bring difficulty to
the reconstruction of phylogenetic tree of Fusarium. There is a need not only to
check substitution rates of genes but also to perform the exact evaluation of
each gene-evolution. RESULTS: We performed phylogenetic analyses based on the
nucleotide sequences of the rDNA cluster region (rDNA cluster), and the beta
tubulin gene (beta-tub), the elongation factor 1alpha gene (EF-1alpha), and the
aminoadipate reductase gene (lys2). Although incongruence of the tree topologies
between lys2 and the other genes was detected, all genes supported the
classification of Fusarium species into 7 major clades, I to VII. To obtain a
reliable phylogeny for Fusarium species, we excluded the lys2 sequences from our
dataset, and re-constructed a maximum likelihood (ML) tree based on the combined
data of the rDNA cluster, beta-tub, and EF-1alpha. Our ML tree indicated some
interesting relationships in the higher and lower taxa of Fusarium species and
related genera. Moreover, we observed a novel evolutionary history of lys2. We
suggest that the unique tree topologies of lys2 are not due to an analytical
artefact, but due to differences in the evolutionary history of genomes caused by
positive selection of particular lineages. CONCLUSION: This study showed the
reliable species tree of the higher and lower taxonomy in the lineage of the
Fusarium genus. Our ML tree clearly indicated 7 major clades within the Fusarium
genus. Furthermore, this study reported differences in the evolutionary histories
among multiple genes within this genus for the first time.
PMID- 22047112
TI - De minimis risk: a proposal for a new category of research risk.
PMID- 22047113
TI - Should the "slow code" be resuscitated?
AB - Most bioethicists and professional medical societies condemn the practice of
"slow codes." The American College of Physicians ethics manual states, "Because
it is deceptive, physicians or nurses should not perform half-hearted
resuscitation efforts ('slow codes')." A leading textbook calls slow codes
"dishonest, crass dissimulation, and unethical." A medical sociologist describes
them as "deplorable, dishonest and inconsistent with established ethical
principles." Nevertheless, we believe that slow codes may be appropriate and
ethically defensible in situations in which cardiopulmonary resuscitation (CPR)
is likely to be ineffective, the family decision makers understand and accept
that death is inevitable, and those family members cannot bring themselves to
consent or even assent to a do-not-resuscitate (DNR) order. In such cases, we
argue, physicians may best serve both the patient and the family by having a
carefully ambiguous discussion about end-of-life options and then providing
resuscitation efforts that are less vigorous or prolonged than usual.
PMID- 22047114
TI - The resuscitation of "slow codes": fraud, lies, and deception.
PMID- 22047115
TI - Quick and limited is better than slow, sloppy, or sly.
PMID- 22047116
TI - Faking it: unnecessary deceptions and the slow code.
PMID- 22047117
TI - What is an "appropriate code"?
PMID- 22047118
TI - Misadventures in CPR: neglecting nonmaleficent and advocacy obligations.
PMID- 22047119
TI - Informed non-dissent: a better option than slow codes when families cannot bear
to say "let her die".
PMID- 22047120
TI - Let's Do Not Resuscitate Placebo Cardiopulmonary Resuscitation.
PMID- 22047121
TI - The false dichotomy: do "everything" or give up.
PMID- 22047122
TI - The "slow code" should be a "no code".
PMID- 22047123
TI - Why not a transparent slow code?
PMID- 22047124
TI - "You don't know me, but ...": access to patient data and subject recruitment in
human subjects research.
PMID- 22047125
TI - The role of cloud computing in managing the deluge of potentially private genetic
data.
PMID- 22047126
TI - Legitimate and ethical: distinguishing when and how regulations apply in patient
oriented research.
PMID- 22047127
TI - Saying privacy, meaning confidentiality.
PMID- 22047128
TI - Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure
akinesia: a case report.
AB - BACKGROUND: Pure akinesia (PA) is a distinct form of parkinsonism characterized
by freezing phenomena. Little is known about brain tumor-associated PA. We
highlight the clinicoradiological changes in a patient with PA and central
nervous system (CNS) metastases of natural killer/T-cell lymphoma (NKTL). CASE
PRESENTATION: A 68-year-old man with stage IVB extranodal NKTL developed a gait
disturbance. Neurological examination of his gait revealed freezing, start
hesitation, short step, forward flexion posture, festination and postural
instability. Mild facial hypomimia and micrographia were observed. There was no
rigidity or tremor in any of the four extremities. Brain magnetic resonance
imaging (MRI) displayed T2-hyperintense lesions in the dorsal brainstem,
cerebellum and periventricular white matter. Diffusion-weighted imaging (DWI) and
the apparent diffusion coefficient (ADC) revealed hyperintensity in these
regions. Cerebrospinal fluid cytology revealed CD56-positive cells on
immunohistochemical staining. The patient's neurological deficits did not respond
to L-dopa treatment and intrathecal administration of methotrexate (MTX). Two
weeks later, he displayed confusion and generalized convulsions. T2-hyperintense
lesions spread to the basal ganglia and the infratentorial regions. Gadolinium
enhancement was observed in the cerebellum and frontal subcortex. DWI and the ADC
revealed diffusion-restricted lesions in the middle cerebellar peduncles, left
internal capsules and cerebral white matter. MTX pulse therapy and intrathecal
administration of cytosine arabinoside and MTX were performed. Two months later,
his ambulatory state was normalized. Brain MRI also revealed marked alleviation
of the infratentorial and supratentorial lesions. CONCLUSIONS: The
clinicoradiological profile of our patient suggested that dorsal ponto
mesencephalic lesions could contribute to the pathogenesis of PA. Physicians
should pay more attention to striking CNS seeding of metastatic NKTL. MTX pulse
therapy had an excellent effect in improving serious symptoms and brain lesions
in our patient.
PMID- 22047129
TI - Kinetically controlled autocatalytic chemical process for bulk production of
bimetallic core-shell structured nanoparticles.
AB - Although bimetallic core@shell structured nanoparticles (NPs) are achieving
prominence due to their multifunctionalities and exceptional catalytic, magnetic,
thermal, and optical properties, the rationale underlying their design remains
unclear. Here we report a kinetically controlled autocatalytic chemical process,
adaptable for use as a general protocol for the fabrication of bimetallic
core@shell structured NPs, in which a sacrificial Cu ultrathin layer is
autocatalytically deposited on a dimensionally stable noble-metal core under
kinetically controlled conditions, which is then displaced to form an active
ultrathin metal-layered shell by redox-transmetalation. Unlike thermodynamically
controlled under-potential deposition processes, this general strategy allows for
the scaling-up of production of high-quality core-shell structured NPs, without
the need for any additional reducing agents and/or electrochemical treatments,
some examples being Pd@Pt, Pt@Pd, Ir@Pt, and Ir@Pd. Having immediate and obvious
commercial potential, Pd@Pt NPs have been systematically characterized by in situ
X-ray absorption, electrochemical-FTIR, transmission electron microscopy, and
electrochemical techniques, both during synthesis and subsequently during testing
in one particularly important catalytic reaction, namely, the oxygen reduction
reaction, which is pivotal in fuel cell operation. It was found that the
bimetallic Pd@Pt NPs exhibited a significantly enhanced electrocatalytic
activity, with respect to this reaction, in comparison with their monometallic
counterparts.
PMID- 22047130
TI - Oral administration of the KATP channel opener diazoxide ameliorates disease
progression in a murine model of multiple sclerosis.
AB - BACKGROUND: Multiple Sclerosis (MS) is an acquired inflammatory demyelinating
disorder of the central nervous system (CNS) and is the leading cause of
nontraumatic disability among young adults. Activated microglial cells are
important effectors of demyelination and neurodegeneration, by secreting
cytokines and others neurotoxic agents. Previous studies have demonstrated that
microglia expresses ATP-sensitive potassium (KATP) channels and its
pharmacological activation can provide neuroprotective and anti-inflammatory
effects. In this study, we have examined the effect of oral administration of
KATP channel opener diazoxide on induced experimental autoimmune
encephalomyelitis (EAE), a mouse model of MS. METHODS: Anti-inflammatory effects
of diazoxide were studied on lipopolysaccharide (LPS) and interferon gamma
(IFNgamma)-activated microglial cells. EAE was induced in C57BL/6J mice by
immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Mice
were orally treated daily with diazoxide or vehicle for 15 days from the day of
EAE symptom onset. Treatment starting at the same time as immunization was also
assayed. Clinical signs of EAE were monitored and histological studies were
performed to analyze tissue damage, demyelination, glial reactivity, axonal loss,
neuronal preservation and lymphocyte infiltration. RESULTS: Diazoxide inhibited
in vitro nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) and
interleukin-6 (IL-6) production and inducible nitric oxide synthase (iNOS)
expression by activated microglia without affecting cyclooxygenase-2 (COX-2)
expression and phagocytosis. Oral treatment of mice with diazoxide ameliorated
EAE clinical signs but did not prevent disease. Histological analysis
demonstrated that diazoxide elicited a significant reduction in myelin and axonal
loss accompanied by a decrease in glial activation and neuronal damage. Diazoxide
did not affect the number of infiltrating lymphocytes positive for CD3 and CD20
in the spinal cord. CONCLUSION: Taken together, these results demonstrate novel
actions of diazoxide as an anti-inflammatory agent, which might contribute to its
beneficial effects on EAE through neuroprotection. Treatment with this widely
used and well-tolerated drug may be a useful therapeutic intervention in
ameliorating MS disease.
PMID- 22047133
TI - Operative Dentistry Home Page.
PMID- 22047135
TI - Online Access.
PMID- 22047131
TI - Low quality of routine microscopy for malaria at different levels of the health
system in Dar es Salaam.
AB - BACKGROUND: Laboratory capacity to confirm malaria cases in Tanzania is low and
presumptive treatment of malaria is being practiced widely. In malaria endemic
areas WHO now recommends systematic laboratory testing when suspecting malaria.
Currently, the use of Rapid Diagnostic Tests (RDTs) is recommended for the
diagnosis of malaria in lower level peripheral facilities, but not in health
centres and hospitals. In this study, the following parameters were evaluated:
(1) the quality of routine microscopy, and (2) the effects of RDT implementation
on the positivity rate of malaria test results at three levels of the health
system in Dar es Salaam, Tanzania. METHODS: During a baseline cross-sectional
survey, routine blood slides were randomly picked from 12 urban public health
facilities in Dar es Salaam, Tanzania. Sensitivity and specificity of routine
slides were assessed against expert microscopy. In March 2007, following training
of health workers, RDTs were introduced in nine public health facilities (three
hospitals, three health centres and three dispensaries) in a near-to-programmatic
way, while three control health facilities continued using microscopy. The
monthly malaria positivity rates (PR) recorded in health statistics registers
were collected before (routine microscopy) and after (routine RDTs) the
intervention in all facilities. RESULTS: At baseline, 53% of blood slides were
reported as positive by the routine laboratories, whereas only 2% were positive
by expert microscopy. Sensitivity of routine microscopy was 71.4% and specificity
was 47.3%. Positive and negative predictive values were 2.8% and 98.7%,
respectively. Median parasitaemia was only three parasites per 200 white blood
cells (WBC) by routine microscopy compared to 1226 parasites per 200 WBC by
expert microscopy. Before RDT implementation, the mean test positivity rates
using routine microscopy were 43% in hospitals, 62% in health centres and 58% in
dispensaries. After RDT implementation, mean positivity rates using routine RDTs
were 6%, 7% and 8%, respectively. The sensitivity and specificity of RDTs using
expert microscopy as reference were 97.0% and 96.8%. The positivity rate of
routine microscopy remained the same in the three control facilities: 71% before
versus 72% after. Two cross-sectional health facility surveys confirmed that the
parasite rate in febrile patients was low in Dar es Salaam during both the rainy
season (13.6%) and the dry season (3.3%). CONCLUSIONS: The quality of routine
microscopy was poor in all health facilities, regardless of their level. Over
diagnosis was massive, with many false positive results reported as very low
parasitaemia (1 to 5 parasites per 200 WBC). RDTs should replace microscopy as
first-line diagnostic tool for malaria in all settings, especially in hospitals
where the potential for saving lives is greatest.
PMID- 22047136
TI - Spectroscopy of HF and HF-containing clusters in solid parahydrogen.
AB - We report measurements of FT-IR absorption spectroscopy of HF, DF, and their
clusters in solid parahydrogen (pH(2)). The observed spectra contain many
absorption lines which were assigned to HF monomers, HF polymers, and clusters
with other species, such as N(2), O(2), orthohydrogen (oH(2)), etc. The
rotational constants of HF and DF monomers were determined from the cooperative
transitions of the vibration of solid pH(2) and the rotation of HF and DF. Small
reduction of the rotational constants indicates that HF and DF are nearly free
rotors in solid pH(2). Time dependence of the spectra suggests that HF and DF
monomers migrate in solid pH(2) and form larger polymers, probably via tunneling
reactions through high energy barriers on inserting another monomer to the
polymers. The line width of HF monomers in solid pH(2) was found to be 4 cm(-1),
which is larger than that of other hydrogen halides in solid pH(2). This broad
line width is explained by rapid rotational relaxation due to the accidental
coincidence between the rotational energy of HF and the phonon energy with
maximum density of states of solid pH(2) and the rotational-translational
coupling in a trapping site.
PMID- 22047137
TI - Low concentrations of honey reduce biofilm formation, quorum sensing, and
virulence in Escherichia coli O157:H7.
AB - Bacterial biofilms are associated with persistent infections due to their high
resistance to antimicrobial agents. Hence, controlling pathogenic biofilm
formation is important in bacteria-related diseases. Honey, at a low
concentration of 0.5% (v/v), significantly reduced biofilm formation in
enterohemorrhagic Escherichia coli O157:H7 without inhibiting the growth of
planktonic cells. Conversely, this concentration did not inhibit commensal E.
coli K-12 biofilm formation. Transcriptome analyses showed that honey
significantly repressed curli genes (csgBAC), quorum sensing genes (AI-2 importer
and indole biosynthesis), and virulence genes (LEE genes). Glucose and fructose
in the honeys were found to be key components in reducing biofilm formation by E.
coli O157:H7 through the suppression of curli production and AI-2 import.
Furthermore, honey, glucose and fructose decreased the colonization of E. coli
O157:H7 cells on human HT-29 epithelial cells. These results suggest that low
concentrations of honey, such as in honeyed water, can be a practical means for
reducing the colonization and virulence of pathogenic E. coli O157:H7.
PMID- 22047138
TI - Room-temperature C-H arylation: merger of Pd-catalyzed C-H functionalization and
visible-light photocatalysis.
AB - This communication describes the development of a room-temperature ligand
directed C-H arylation reaction using aryldiazonium salts. This was achieved by
the successful merger of palladium-catalyzed C-H functionalization and visible
light photoredox catalysis. The new method is general for a variety of directing
groups and tolerates many common functional groups.
PMID- 22047139
TI - RNA-Seq reveals genotype-specific molecular responses to water deficit in
eucalyptus.
AB - BACKGROUND: In a context of climate change, phenotypic plasticity provides long
lived species, such as trees, with the means to adapt to environmental variations
occurring within a single generation. In eucalyptus plantations, water
availability is a key factor limiting productivity. However, the molecular
mechanisms underlying the adaptation of eucalyptus to water shortage remain
unclear. In this study, we compared the molecular responses of two commercial
eucalyptus hybrids during the dry season. Both hybrids differ in productivity
when grown under water deficit. RESULTS: Pyrosequencing of RNA extracted from
shoot apices provided extensive transcriptome coverage - a catalog of 129,993
unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million
base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably
existing Eucalyptus EST collections, adding 36,985 unigenes not previously
represented. Digital analysis of read abundance in 14,460 contigs identified
1,280 that were differentially expressed between the two genotypes, 155 contigs
showing differential expression between treatments (irrigated vs. non irrigated
conditions during the dry season), and 274 contigs with significant genotype-by
treatment interaction. The more productive genotype displayed a larger set of
genes responding to water stress. Moreover, stress signal transduction seemed to
involve different pathways in the two genotypes, suggesting that water shortage
induces distinct cellular stress cascades. Similarly, the response of functional
proteins also varied widely between genotypes: the most productive genotype
decreased expression of genes related to photosystem, transport and secondary
metabolism, whereas genes related to primary metabolism and cell organisation
were over-expressed. CONCLUSIONS: For the most productive genotype, the ability
to express a broader set of genes in response to water availability appears to be
a key characteristic in the maintenance of biomass growth during the dry season.
Its strategy may involve a decrease of photosynthetic activity during the dry
season associated with resources reallocation through major changes in the
expression of primary metabolism associated genes. Further efforts will be needed
to assess the adaptive nature of the genes highlighted in this study.
PMID- 22047140
TI - Laccase-carrying electrospun fibrous membranes for adsorption and degradation of
PAHs in shoal soils.
AB - The removal of polycyclic aromatic hydrocarbons (PAHs) from soil is costly and
time-consuming. The high hydrophobicity of PAHs makes PAH diffusion from soil
particles by hydraulic flow difficult. The phase transfer of PAHs from soil to
another available mediator is crucial for PAH removal. This study focuses on the
remediation of PAH-contaminated shoal soil, located in Yangtze, China, using
three types of laccase-carrying electrospun fibrous membranes (LCEFMs) fabricated
via emulsion electrospinning. These LCEFMs were composed of core-shell structural
nanofibers (for PAH adsorption), with laccase in the core (for PAH degradation)
and pores on the shell (for mass transfer). The LCEFMs with strong adsorptivity
extracted the PAHs from the soil particles, resulting in an obvious enhancement
of PAH degradation. The removal efficiencies in 6 h for phenanthrene,
fluoranthene, benz[a]anthracene and benzo[a]pyrene were greater than 95.1%,
93.2%, 79.1%, and 72.5%, respectively. The removal half-lives were 0.003-1.52 h,
much shorter than those by free laccase (17.9-67.9 h) or membrane adsorption
(1.25-12.50 h). The third-order reaction kinetics suggested that the superficial
adsorption and internal diffusion were the rate-limiting steps of the overall
reaction. A synergistic effect between adsorption and degradation was also
proposed on the basis of the triple phase distribution and kinetics analyses.
PMID- 22047141
TI - Generation and characterization of transgenic mice expressing mitochondrial
targeted red fluorescent protein selectively in neurons: modeling
mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis.
AB - BACKGROUND: Mitochondria have roles or appear to have roles in the pathogenesis
of several chronic age-related and acute neurological disorders, including
Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease,
and cerebral ischemia, and could be critical targets for development of rational
mechanism-based, disease-modifying therapeutics for treating these disorders
effectively. A deeper understanding of neural tissue mitochondria pathobiologies
as definitive mediators of neural injury, disease, and cell death merits further
study, and the development of additional tools to study neural mitochondria will
help achieve this unmet need. RESULTS: We created transgenic mice that express
the coral (Discosoma sp.) red fluorescent protein DsRed2 specifically in
mitochondria of neurons using a construct engineered with a Thy1 promoter,
specific for neuron expression, to drive expression of a fusion protein of DsRed2
with a mitochondrial targeting sequence. The biochemical and histological
characterization of these mice shows the expression of mitochondrial-targeted
DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions,
including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red
fluorescent mitochondria were visualized in cerebral cortical and hippocampal
pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal
motor neurons. For the purpose of proof of principle application, these mice were
used in excitotoxicity paradigms and double transgenic mice were generated by
crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP)
under the control of the Hlxb9 promoter that drives eGFP expression specifically
in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral
sclerosis (ALS) mice expressing human mutant superoxide dismutase-1. CONCLUSIONS:
These novel transgenic mice will be a useful tool for better understanding the
biology of mitochondria in mouse and cellular models of human neurological
disorders as exemplified by the mitochondrial swelling and fission seen in
excitotoxicity and mouse ALS.
PMID- 22047142
TI - Contralateral inguinal hernia after negative laparoscopic evaluation: a rare but
real phenomenon.
AB - BACKGROUND: The procedure of inguinal herniorrhaphy is the most common procedure
performed by pediatric surgeons today. Laparoscopy has proved to be both
sensitive and specific for evaluating the contralateral inguinal region. Despite
the attractiveness that transinguinal laparoscopy offers and the success it has
seen, we report a series of hernias after the utilization of this tool. METHODS:
After IRB approval, a retrospective review of our institutions' experience from
1/2002 to 6/2010 with children who underwent unilateral inguinal hernia repair
with contralateral evaluation with laparoscopy was completed. Data recorded
included sex, age of initial presentation, laterality of initial hernia, age at
second presentation, and operative time of initial surgery. RESULTS: From 2002 to
2010, 1291 patients underwent unilateral inguinal hernia repair with negative
laparoscopic evaluation of the opposite ring. There were 32 patients (2.5%) who
subsequently presented with an inguinal hernia on the contralateral side. All
were men. The average age of initial presentation was 42.7 months. The mean time
to occurrence of the contralateral hernia was found to be 16.7 months with a
median of 12.2 months. The mean operative time for the initial operation was
found to be 25.6 minutes. CONCLUSIONS: When using laparoscopy to explore the
contralateral inguinal region, the surgeon should be aware that a negative exam
may still be associated with a small chance of clinically developing a hernia.
PMID- 22047143
TI - Single-incision laparoscopic colon and rectal surgery for pediatric inflammatory
bowel disease and polyposis syndromes.
AB - BACKGROUND: Minimally invasive procedures for inflammatory bowel disease have
been shown to improve recovery in children. We report our initial experience with
single-incision laparoscopic operations for pediatric intestinal disease.
METHODS: We retrospectively reviewed 12 procedures in 11 patients (4 women) from
March 2010 to January 2011. Procedures were conducted by using standard
laparoscopic instruments. RESULTS: Mean age was 15 years (9-17 years). Procedures
included three total abdominal colectomies, four two-stage ileal-pouch anal
anastomosis (IPAA), two single-stage IPAA, two three-stage IPAA, and one
ileocectomy. An accessory umbilical port was used in 6 cases. Mean operating time
was 287 minutes. Mean length of stay was 4.1 days (3-9 days). Postoperative
complications have occurred in 5 patients (42%). Anastomotic leak occurred in 2
patients with IPAA without protective ileostomy, 1 operative small bowel
obstruction, 1 pelvic abscess and portal vein thrombosis, and 1 readmission for
dehydration. Both patients who had leaked have recovered well and had their
stomas reversed. Mean follow-up is 190 days. Average number of daily bowel
movements is 4.5. Pouchitis has occurred in 50% (4/8) of patients. CONCLUSIONS:
Single-incision laparoscopic surgery for pediatric intestinal disease is safe and
feasible by using standard laparoscopic instruments. We do not advocate IPAA
without a stoma due to the high rate of anastomotic leak. Continued experience
will shorten operative times and reduce complications.
PMID- 22047144
TI - The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6).
AB - The human kallikrein-related peptidase 6 (KLK6) gene belongs to the 15-member
kallikrein (KLK) gene family mapping to chromosome 19q13.3-13.4. Encoding for an
enzyme with trypsin-like properties, KLK6 can degrade components of the
extracellular matrix. The successful utilisation of another KLK member (KLK3/PSA)
for prostate cancer diagnosis has led many to evaluate KLK6 as a potential
biomarker for other cancer and diseased states. The observed dysregulated
expression in cancers, neurodegenerative diseases and skin conditions has led to
the discovery that KLK6 participates in other cellular pathways including
inflammation, receptor activation and regulation of apoptosis. Moreover, the
improvements in high-throughput genomics have not only enabled the identification
of sequence polymorphisms, but of transcript variants, whose functional
significances have yet to be realised. This comprehensive review will summarise
the current findings of KLK6 pathophysiology and discuss its potential as a
viable biomarker.
PMID- 22047145
TI - The effect of hematocrit on the results of measurements using glucose meters
based on different techniques.
AB - BACKGROUND: The aim of the study was to evaluate the effect of hematocrit (HCT)
on glucose meter assays based on different measurement techniques. METHODS: This
paper studied glucose meters utilizing the glucose dehydrogenase reaction and
four measurement techniques: colorimetry (HemoCue), reflectometry (Accu-Chek
Active), amperometry (Optium Xido) and coulometry (Optium Omega). The EDTA venous
blood samples HCT were modified by adding or removing defined aliquots of plasma.
Glucose concentration was measured using each meter in 27 batches of blood
samples, with HCT ranging from 20% to 60% in 10% increments. The data were
analyzed using repeated measures models and a linear random effects model.
RESULTS: A significant relationship between HCT and glucose reading in all meters
was found and, for all meters except Optium Xido, there was a significant
modification of this relationship by glucose level. The relative decrease in
glucose concentration per 1% increase of the HCT value varied from 0.30% for
Optium Omega in samples with glucose concentrations <5.55 mmol/L to 1.37% for
Optium Xido in the same stratum (p<0.0001). The 5% glucose meter error (the ADA
recommendation) was reached in the <5.55 mmol/L stratum after HCT change by 3.9%
16.7%. CONCLUSIONS: There is a significant continuous effect of HCT on
measurement accuracy of glucose meters across its wide range of values and
glucose concentrations. The most sensitive to the HCT interference was the system
utilizing amperometric technique (Optium Xido) followed by the one with
reflectometric technique (Accu-Chek Active), while the systems with the
coulometric technique (Optium Omega) or colorimetric measurements in whole blood
haemolysate (HemoCue) were less sensitive.
PMID- 22047146
TI - High resolution time-of-flight mass analysis of the entire range of intact singly
charged proteins.
AB - The proof of principle for high-resolution analysis of intact singly charged
proteins of any size is presented. Singly charged protein ions were produced by
electrospray ionization followed by surface-induced charge reduction at
atmospheric pressure. The inlet and trapping system "stops" the forward momentum
of the protein ions over a very broad range to be captured by the digitally
produced electric fields of a large radius linear ion trap whereupon they are
moved into a smaller radius linear ion trap and collected and concentrated in
front of its exit end-cap electrode using digital waveform manipulation. The
protein ions are then ejected on demand from the end of the small radius linear
quadrupole in a tightly collimated ion beam with an instrumentally defined
kinetic energy into the acceleration region of an orthogonal acceleration
reflectron time-of-flight mass analyzer where their flight times were measured
and detected with a Photonis BiPolar TOF detector. We present results that
clearly prove that massive singly charged ions can yield high-resolution mass
spectra with very low chemical noise and without loss of sensitivity with
increasing mass across the entire spectrum. Analysis of noncovalently bound
protein complexes was demonstrated with streptavidin-Cy5 bound with a
biotinylated peptide mimic. Our results suggest proteins across the entire range
can be directly quantified using our mass analysis technique. We present evidence
that solvent molecules noncovalently adduct onto the proteins while yielding
consistent flight time distributions. Finally, we provide a look into future that
will result from the ability to rapidly measure and quantify protein
distributions.
PMID- 22047147
TI - Bruce B Smith 1917-2007.
PMID- 22047152
TI - Protein array diagnostics for guiding therapy in rheumatoid arthritis.
AB - Early diagnosis and effective management of rheumatoid arthritis (RA) are
pivotal, given the progressive, chronic, inflammatory, multi-systemic nature of
the disease. Currently, proper initiation of adequate, individually tailored
interventions in RA is delayed by the difficulty of early diagnosis and the
limitations of disease activity and therapeutic response assessment tools. This
is a significant challenge to rheumatologists, further complicated by the dynamic
and progressively evolving autoimmune nature of RA, which is characterized by
several immune mediators in a complex network that regulates the perpetuation of
inflammation. Protein arrays constitute the most advanced current technology that
can provide a comprehensive parallel analysis of this diverse network in RA,
providing an individualized insight into immune status and host immune response.
The last few years have seen significant transitions in the field of protein
arrays, demonstrated by a technologic shift from the bench to the bedside, paving
the way for the medical and scientific community to deliver patient-specific
assessments and personalized management. Screening of protein arrays with sera or
tissues from patients with RA enables the probing of immune responses and the
identification of autoantibody signatures that can be used for the diagnosis and
therapeutic management of patients. This article reviews the technology and the
applications for protein arrays in the diagnosis and prognosis of RA. Clinical
assessment tools could be derived from protein arrays, which may provide a means
to continually track patients, allowing better evaluation of intervention
strategies on a patient-specific basis and identification of diagnostic and
disease activity biomarkers that could be used to guide optimal therapy in RA.
PMID- 22047153
TI - Genotype-based dosing algorithms for warfarin therapy: data review and
recommendations.
AB - Warfarin, the most common oral anticoagulant, is the ideal candidate for
pharmacogenetic dosing and gene-based 'individualization' of care. A plethora of
studies have shown that stable dose requirements can be predicted using sequence
variants in the CYP2C9 and VKORC1 genes in both sexes and in different races.
Multiple clinical trials of pharmacogenetic warfarin dosing have been conducted
with various methods, including several randomized trials that have been
completed. These studies have reported varying degrees of success and some have
been met with substantial skepticism. Other much larger randomized trials are
ongoing. This paper reviews and synthesizes the various clinical trials that have
been published and touches on the potential that the ongoing trials offer. The
emergence of new oral anticoagulants also raises the question of the relevance of
pharmacogenetic warfarin dosing for the future. The cost of genotype-guided
dosing is substantial, and none of the studies to date have shown a cost-benefit
of using pharmacogenetic warfarin dosing in clinical practice. Although
pharmacogenetics-guided warfarin dosing has been discussed for many years, the
currently available data regarding this genetically individualized dosing suggest
that pharmacogenetics remains unproven for use in clinical warfarin prescription.
PMID- 22047154
TI - Review of the relationship between C-reactive protein and exercise.
AB - C-reactive protein (CRP), an acute phase reactant, is associated with systemic
inflammation. Many studies have demonstrated that CRP levels have important
prognostic implications for patients. For example, individuals with elevated CRP
levels have an increased risk of cardiovascular events. The JUPITER study showed
that reducing CRP levels can mitigate this risk. Various trials have investigated
the effect of lifestyle modifications on serum CRP levels. Specifically, the
impact of different exercise-based protocols on CRP levels has been researched.
This review article evaluates the response of CRP levels to aerobic-based,
resistance-based, and combination exercise protocols. Furthermore, it examines
the impact of such regimens in children, adults, and the elderly. No definitive
answers exist regarding the relationship between exercise and CRP levels.
Significant reductions in CRP levels were noted in 11 of 25 trials of aerobic
based regimens, two of five studies of combination protocols, and neither of two
trials of resistance-based regimens. Similar findings were seen across all age
groups. There were significant CRP reductions in nine of 18 adult studies, four
of ten child studies, and one of three elderly studies. Mixed results reflect
uncertainty about the ability of exercise to reduce inflammation. Various
mechanisms, including increased protein synthesis and fat loss, have been
proposed to explain the potential anti-inflammatory effects of exercise. While
exercise-based regimens have produced inconsistent results, lifestyle
modifications do appear to have significant anti-inflammatory effects. This was
particularly evident in studies that utilized combined diet/exercise programs.
Significant CRP reductions were seen in five of seven such trials. Interestingly,
both studies with failed combination protocols achieved substantial CRP
reductions in their diet-only groups. These findings suggest that weight loss is
important in reducing inflammation. Additionally, they indicate that combined
diet/exercise protocols should be part of any lifestyle intervention program.
Further research will be needed to identify optimal regimens for achieving anti
inflammatory benefits.
PMID- 22047155
TI - Development of multiplex PCR method for the analysis of glutathione s-transferase
polymorphism.
AB - BACKGROUND: Busulfan is a key compound in myeloablative chemotherapy before
hematopoietic stem-cell transplantation in children. Genetic polymorphisms of
glutathione S-transferase (GST), which is involved in the metabolism of busulfan,
have been implicated in interindividual variability in busulfan pharmacokinetics.
Development of a rapid and simplified method for polygenic analysis of GST may
facilitate large pharmacogenetic studies and clinical application of
individualized busulfan dose adjustment. We previously introduced an effective
PCR method for analyzing multiple genes using a small amount of DNA, termed
'TotalPlex amplification'. OBJECTIVE: The aim of this study was to extend the
application of the TotalPlex method to the specific GST gene families (A1, P1,
M1, and T1) that are related to busulfan metabolism, and thereby facilitate
pharmacogenetic analysis of GST polymorphisms. METHODS: Seven genetic
polymorphisms (GSTA1 promoter -52G>A, -69C>T, -567T>G, and -631T>G; GSTP1 313A>G;
GSTM1 deletion; and GSTT1 deletion) were analyzed by multiplex PCR and
genotyping, and the genotyping results from TotalPlex were verified with those
from uniplex PCR. RESULTS: Using five pairs of specific bulging-specific primers,
seven specific gene fragments were successfully amplified by multiplex
amplification coupled to a multiplexed bead array detection system, with a
smaller amount of DNA and a shorter process time than is needed for the
conventional approach. The genotypes of seven loci from 30 different genomic DNA
samples derived using the multiplex system were consistent with the results of
standard genotyping methods. CONCLUSION: Our multiplex system provides a fast,
inexpensive, and accurate method of detecting multiple GST polymorphisms (GSTA1,
GSTP1, GSTM1, and GSTT1).
PMID- 22047156
TI - Phenotypic analysis of HIV-1 genotypic drug-resistant isolates from China, using
a single-cycle system.
AB - BACKGROUND AND OBJECTIVES: Drug resistance in HIV-1 is one of the main causes of
failure of antiretroviral therapy. Phenotypic detection of drug-resistant HIV-1
can provide guidance in selecting the optimal treatment regimen. Traditional
phenotype assays are labor intensive and time consuming. Thus, a rapid and
convenient phenotype assay with a single cycle of replication was developed and
used in this study. METHODS: Two restriction endonuclease sites, ApaI and AgeI,
were inserted into the plasmid pSG3Deltaenv(,) using site-directed mutagenesis.
The reverse transcriptase and protease genes of HIV-1 were amplified from
patients and cloned into the modified pSG3Deltaenv. Sixteen original recombinant
pseudoviruses were generated. The phenotypic susceptibility of these 16
recombinant pseudoviruses to 12 antiretroviral drugs was determined using a
luciferase reporter system, and the phenotype and genotype results were compared.
RESULTS: A modified phenotype assay with a single-cycle system was established,
and its reproducibility and feasibility were validated. Approximately 89% of the
phenotype results were in agreement with the genotype results; this slight
disagreement may have been due to complex and multiple resistance mutations. The
phenotype results showed that individual pseudoviruses with four thymidine analog
mutations (TAMs).[M41L, T67N, L210W, and T215Y] in combination with various other
mutations had different levels of resistance to nucleoside reverse transcriptase
inhibitors (NRTIs). Mutations E44A, T69D, and V118I influenced the pattern of
resistance of TAMs. The level of resistance to non-NRTIs (NNRTIs) was also
variable when different NNRTI-resistance mutations were combined. CONCLUSION: The
single-cycle pseudovirus phenotypic susceptibility detection system reflects HIV
1 drug resistance, especially for complex resistance mutants, and could be used
to screen new antiretroviral candidates.
PMID- 22047158
TI - Biochemical properties of bioplastics made from wheat gliadins cross-linked with
cinnamaldehyde.
AB - The aim of this work has been to study the modification of gliadin films with
cinnamaldehyde as a potential cross-linker agent. The molecular weight profile
and cross-linking density showed that cinnamaldehyde increased reticulation in
the resulting films. The participation of free amino groups of the protein in the
newly created entanglements could be a possible mechanism of connection between
the polypeptidic chains. The combination of a Schiff base and a Michael addition
is a feasible approach to understanding this mechanism. The protein solubility in
different media pointed to lower participation by both noncovalent and disulfide
bonds in stabilizing the structure of the cross-linked films. The new covalent
bonds formed by the cinnamaldehyde treatment hampered water absorption and weight
loss, leading to more water-resistant matrices which had not disintegrated after
5 months. The properties of this novel bioplastic could be modified to suit the
intended application by using cinnamaldehyde, a naturally occurring compound.
PMID- 22047159
TI - Influence of Bifidobacterium bifidum on release of minerals from bread with
differing bran content.
AB - Bread is considered an important source of minerals; however, the presence of
fiber and phytic acid reduces bioavailability of minerals from cereal products.
It is well established that activity of microorganisms in human gut increases the
amount of nutrients released during digestion. The aim of this study was to
determine the influence of Bifidobacterium bifidum on release of some minerals
from bread using an in vitro process of enzymatic digestion. White bread and with
addition of 15, 30, or 45% of bran was baked in a bakery by traditional methods,
with addition of yeasts and rye leaven, from flour made of wheat, Tonacja
variety. Concentrations of calcium, magnesium, manganese, zinc, copper, and iron
were determined by atomic absorption spectrometry. Bread was enzymatically
digested in vitro without and with the addition of Bifidobacterium bifidum KD6
(inoculum 10(6) CFU/cm(3)) and percentages of minerals released were determined.
The concentration of minerals released during enzymatic digestion varied
depending upon the element, quantity of bran, and presence of bacteria. Increase
in bran content decreased release of elements. Bifidobacterium bifidum KD6
enhanced amounts of magnesium and zinc released from all types of bread, while
manganese and copper rose only from white bread with 15% bran addition. Bacteria
decreased amounts of calcium and iron released from bread. Data indicate that
diets rich in beneficial bacteria (probiotics) but not balanced with minerals
might increase mineral deficiency.
PMID- 22047160
TI - Translational research to develop a human PBPK models tool kit-volatile organic
compounds (VOCs).
AB - Toxicity and exposure evaluations remain the two of the key components of human
health assessment. While improvement in exposure assessment relies on a better
understanding of human behavior patterns, toxicity assessment still relies to a
great extent on animal toxicity testing and human epidemiological studies. Recent
advances in computer modeling of the dose-response relationship and distribution
of xenobiotics in humans to important target tissues have advanced our abilities
to assess toxicity. In particular, physiologically based pharmacokinetic (PBPK)
models are among the tools than can enhance toxicity assessment accuracy. Many
PBPK models are available to the health assessor, but most are so difficult to
use that health assessors rarely use them. To encourage their use these models
need to have transparent and user-friendly formats. To this end the Agency for
Toxic Substances and Disease Registry (ATSDR) is using translational research to
increase PBPK model accessibility, understandability, and use in the site
specific health assessment arena. The agency has initiated development of a human
PBPK tool-kit for certain high priority pollutants. The tool kit comprises a
series of suitable models. The models are recoded in a single computer simulation
language and evaluated for use by health assessors. While not necessarily being
state-of-the-art code for each chemical, the models will be sufficiently accurate
to use for screening purposes. This article presents a generic, seven-compartment
PBPK model for six priority volatile organic compounds (VOCs): benzene (BEN),
carbon tetrachloride (CCl(4)), dichloromethane (DCM), perchloroethylene (PCE),
trichloroethylene (TCE), and vinyl chloride (VC). Limited comparisons of the
generic and original model predictions to published kinetic data were conducted.
A goodness of fit was determined by calculating the means of the sum of the
squared differences (MSSDs) for simulation vs. experimental kinetic data using
the generic and original models. Using simplified solvent exposure assumptions
for oral ingestion and inhalation, steady-state blood concentrations of each
solvent were simulated for exposures equivalent to the ATSDR Minimal Risk Levels
(MRLs). The predicted blood levels were then compared to those reported in the
National Health and Nutrition Examination Survey (NHANES). With the notable
exception of BEN, simulations of combined oral and inhalation MRLs using our
generic VOC model yielded blood concentrations well above those reported for the
95th percentile blood concentrations for the U.S. populations, suggesting no
health concerns. When the PBPK tool kit is fully developed, risk assessors will
have a readily accessible tool for evaluating human exposure to a variety of
environmental pollutants.
PMID- 22047161
TI - Evaluation of the interactions between multiwalled carbon nanotubes and Caco-2
cells.
AB - The aim of this study was to determine whether multiwalled carbon nanotubes
(MWNCT) are taken up by and are toxic to human intestinal enterocytes using the
Caco-2 cell model. Caco-2 cells were exposed to 50 MUg/ml MWCNT (oxidized or
pristine) for 24 h, and experiments were repeated in the presence of 2.5 mg/L
natural organic matter. Cells displayed many of the properties that characterize
enterocytes, such as apical microvilli, basolateral basement membrane, and
glycogen. The cell monolayers also displayed tight junctions and electrical
resistance. Exposure to pristine and oxidized MWCNT, with or without natural
organic matter, did not markedly affect viability, which was assessed by
measuring activity of released lactate dehydrogenase (LDH) and staining with
propidium iodide. Ultrastructural analysis revealed some damage to microvilli
colocalized with the MWCNT; however, neither type of MWCNT was taken up by Caco-2
cells. In contrast, pristine and oxidized MWCNT were taken up by the macrophage
RAW 264.7 line. Our study suggests that intestinal enterocytes cells do not take
up MWCNT.
PMID- 22047163
TI - Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse
skin.
AB - Recent data, using a murine model, have indicated that dermal exposure to
perfluorooctanoic acid (PFOA) induces immune modulation, suggesting that this may
be an important route of PFOA exposure. To investigate the dermal penetration
potential of PFOA, serum concentrations were analyzed in mice following topical
application. Statistically significant and dose-responsive increases in serum
PFOA concentrations were identified. In vitro dermal penetration studies also
demonstrated that PFOA permeates both mouse and human skin. Investigation into
the mechanisms mediating PFOA penetration demonstrated that dermal absorption was
strongly dependent upon the ionization status of PFOA. In addition, PFOA solid,
but not 1% PFOA/acetone solution, was identified as corrosive using a cultured
epidermis in vitro model. Despite its corrosive potential, expression of
inflammatory cytokines in the skin of topically exposed mice was not altered.
These data suggest that PFOA is dermally absorbed and that under certain
conditions the skin may be a significant route of exposure.
PMID- 22047162
TI - Indigenous American ancestry is associated with arsenic methylation efficiency in
an admixed population of northwest Mexico.
AB - Many studies provide evidence relating lower human arsenic (As) methylation
efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)),
with several As-induced diseases, possibly due to the fact that MMA(V) serves as
a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies
suggested that indigenous Americans (AME) methylate As more efficiently; however,
data supporting this have been equivocal. The aim of this study was to
characterize the association between AME ancestry and As methylation efficiency
using a panel of ancestry informative genetic markers to determine individual
ancestry proportions in an admixed population (composed of two or more isolated
ancestral populations) of 746 individuals environmentally exposed to As in
northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3-1053.5
MUg/L, while percent AME (%AME) mean and range were 72.4 and 23-100. Adjusted
(gender, age, AS3MT 7388/M287T haplotypes, body mass index [BMI], and TAs)
multiple regression model showed that higher AME ancestry is significantly
associated with lower percentage of urinary As excreted as MMA(V) (%uMMA) in this
population (p < .01). Data also demonstrated a significant interaction between
BMI and gender, indicating negative association between BMI and %uMMA, stronger
in women than men (p < .01). Moreover, age and the AS3MT variants 7388 (intronic)
and M287T (nonsynonymous) were also significantly associated with As methylation
efficiency (p < .01). This study highlights the importance of BMI and indigenous
American ancestry in some of the observed variability in As methylation
efficiency, underscoring the need to be considered in epidemiology studies,
particularly those carried out in admixed populations.
PMID- 22047164
TI - Errors of alternative medicine: lessons for general practice.
PMID- 22047165
TI - IPCRG: International Primary Care Respiratory Group.
PMID- 22047166
TI - Hyperbaric oxygen and N-acetylcysteine treatment in L-arginine-induced acute
pancreatitis in rats.
AB - BACKGROUND: This study was designed to evaluate the combined effects of
hyperbaric oxygen (HBO) and N-acetylcysteine (NAC) on acute necrotizing
pancreatitis in rats. METHODS: Experiments were performed in 50 male Wistar rats,
which were divided into five groups (N = 10 for each group). The first group
received normal saline (0.9% NaCl) intraperitoneal and served as the control
group. In the second group, acute pancreatitis was induced by 3.2-g/kg body
weight L-arginine intraperitoneal twice at an interval of 1 hr, which has been
shown previously to produce severe necrotizing acute pancreatitis. In the third
group, NAC treatment (1000 mg/kg) was given after 1 hr of the induction of acute
pancreatitis twice 24 hr apart. In the fourth group, animals received HBO, 6 hr
after the induction of pancreatitis twice 12 hr apart. In the fifth group,
animals received together NAC as in Group 3 and HBO treatment as in Group 4.
Groups 1, 2, and 3 were left under normal atmospheric pressures. Twelve hours
after last treatment, the animals were killed by exsanguinations. Blood samples
were studied for amylase, calcium, and lactate dehydrogenase (LDH), pancreatic
histology, pancreatic tissue malondialdehyde, superoxide dismutase, and
glutathione levels. RESULTS: Acute pancreatitis is reduced by the treatment of
NAC, HBO, NAC + HBO. HBO + NAC groups performed statistically the best in
preventing L-arginine-induced acute necrotising pancreatitis. CONCLUSIONS: NAC
especially combined with HBO, decreases oxidative stress parameters, serum
amylase, calcium, and LDH levels, as well as histopathologic score.
PMID- 22047167
TI - Maternal exposure to air pollution before and during pregnancy related to changes
in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort.
AB - BACKGROUND: Toxicants can cross the placenta and expose the developing fetus to
chemical contamination leading to possible adverse health effects, by potentially
inducing alterations in immune competence. Our aim was to investigate the impacts
of maternal exposure to air pollution before and during pregnancy on newborn's
immune system. METHODS: Exposure to background particulate matter less than 10
MUm in diameter (PM10) and nitrogen dioxide (NO2) was assessed in 370 women three
months before and during pregnancy using monitoring stations. Personal exposure
to four volatile organic compounds (VOCs) was measured in a subsample of 56 non
smoking women with a diffusive air sampler during the second trimester of
pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to
determine lymphocyte subsets. RESULTS: Among other immunophenotypic changes in
cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01),
0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 MUg/m3 increase
in PM10 levels three months before and during the first, second and third
trimester of pregnancy, respectively, were observed after adjusting for
confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in
association with personal exposure to benzene. A similar trend was observed
between NO2 exposure and CD4+CD25+ T-cell percentage; however the association was
stronger between NO2 exposure and an increased percentage of CD8+ T-cells.
CONCLUSIONS: These data suggest that maternal exposure to air pollution before
and during pregnancy may alter the immune competence in offspring thus increasing
the child's risk of developing health conditions later in life, including asthma
and allergies.
PMID- 22047168
TI - Photonic control of surface anchoring on solid colloids dispersed in liquid
crystals.
AB - The anchoring of liquid-crystal (LC) mesogens to the surfaces of colloids is an
important factor in determining intercolloidal interactions and the symmetry of
the ensuing colloidal assembly in nematic colloids. The dynamic control of
surface anchoring could therefore provide a handle to tune the colloidal
organization and resulting properties in these systems. In this article, we
report our results on the study of thermotropic nematic LC (E7) dispersions of
silica and glass microcolloids bearing photosensitive surface azobenzene groups.
By the photoinduced modulation of the colloidal-LC interfacial properties, due to
the trans-cis isomerization of azobenzene units, we tune the anchoring on silica
colloids from homeotropic (trans-azobenzene) to homogeneous planar (cis
azobenzene) reversibly. In tune with the change in surface anchoring, the
interparticle interactions were also dictated by dipolar and quadrupolar
symmetries for homeotropic and homogeneous planar anchoring, respectively. In our
experiments, we find that, in addition to the isomerization state of the surface
bound azobenzene units, the nature of the colloid plays a crucial role in
determining the anchoring state obtained on applying photostimuli. We also study
the LC anchoring on colloids as a function of the azobenzene surface density and
find that beyond a threshold value the anchoring properties remain invariant.
PMID- 22047169
TI - Self-assembling of zinc phthalocyanines on ZnO (1010) surface through multiple
time scales.
AB - We adopt a hierarchic combination of theoretical methods to study the assembling
of zinc phthalocyanines (ZnPcs) on a ZnO (1010) surface through multiple time
scales. Atomistic simulations, such as model potential molecular dynamics and
metadynamics, are used to study the energetics and short time evolution (up to
~100 ns) of small ZnPc aggregates. The stability and the lifetime of large
clusters is then studied by means of an atomistically informed coarse-grained
model using classical molecular dynamics. Finally, the macroscopic time scale
clustering phenomenon is studied by Metropolis Monte Carlo algorithms as a
function of temperature and surface coverage. We provide evidence that at room
temperature the aggregation is likely to occur at sufficiently high coverage, and
we characterize the nature, morphology, and lifetime of ZnPc's clusters. We
identify the molecular stripes oriented along [010] crystallographic directions
as the most energetically stable aggregates.
PMID- 22047171
TI - Comparative reactivity of ferric-superoxo and ferryl-oxo species in heme and non
heme complexes.
AB - Ferryl-oxo species have been recognized as a key oxidant in many heme and non
heme enzymes. Recently, less-characterized ferric-superoxo species have been
found or suggested to be another electrophilic oxidant. Reactivity of several
vital ferryl-oxo and ferric-superoxo model complexes was examined by DFT
calculations. Reactivity is found to correlate well with thermodynamic driving
force and can increase with higher electrophilicity of the oxidant. Reactivity of
the ferric-superoxo oxidants generally is not "superior" to the ferryl-oxo ones.
Compared to the high-spin non-heme ferric-superoxo, the lower reactivity of low
spin heme ferric-superoxo, seldom utilized in nature, can be attributed to lower
electrophilicity and more pronounced quenching of anti-ferromagnetic coupling
between the ferric and superoxo parts. The present comparison should shed some
light on mechanistic strategies in heme and non-heme enzymes and provide clues to
rational design of ferric-superoxo oxidants.
PMID- 22047170
TI - The contribution of activated astrocytes to Abeta production: implications for
Alzheimer's disease pathogenesis.
AB - BACKGROUND: beta-Amyloid (Abeta) plays a central role in Alzheimer's disease (AD)
pathogenesis. Neurons are major sources of Abeta in the brain. However,
astrocytes outnumber neurons by at least five-fold. Thus, even a small level of
astrocytic Abeta production could make a significant contribution to Abeta burden
in AD. Moreover, activated astrocytes may increase Abeta generation. beta-Site
APP cleaving enzyme 1 (BACE1) cleavage of amyloid precursor protein (APP)
initiates Abeta production. Here, we explored whether pro-inflammatory cytokines
or Abeta42 would increase astrocytic levels of BACE1, APP, and beta-secretase
processing, implying a feed-forward mechanism of astrocytic Abeta production.
METHODS: Mouse primary astrocytes were treated with combinations of LPS, TNF
alpha, IFN-gamma, and IL-1beta and analyzed by immunoblot and ELISA for
endogenous BACE1, APP, and secreted Abeta40 levels. Inhibition of JAK and iNOS
signaling in TNF-alpha+IFN-gamma-stimulated astrocytes was also analyzed. In
addition, C57BL/6J or Tg2576 mouse astrocytes were treated with oligomeric or
fibrillar Abeta42 and analyzed by immunoblot for levels of BACE1, APP, and
APPsbetasw. Astrocytic BACE1 and APP mRNA levels were measured by TaqMan RT-PCR.
RESULTS: TNF-alpha+IFN-gamma stimulation significantly increased levels of
astrocytic BACE1, APP, and secreted Abeta40. BACE1 and APP elevations were post
transcriptional at early time-points, but became transcriptional with longer TNF
alpha+IFN-gamma treatment. Despite a ~4-fold increase in astrocytic BACE1 protein
level following TNF-alpha+IFN-gamma stimulation, BACE1 mRNA level was
significantly decreased suggesting a post-transcriptional mechanism. Inhibition
of iNOS and JAK did not reduce TNF-alpha+IFN-gamma-stimulated elevation of
astrocytic BACE1, APP, and Abeta40, except that JAK inhibition blocked the APP
increase. Finally, oligomeric and fibrillar Abeta42 dramatically increased levels
of astrocytic BACE1, APP, and APPsbetasw through transcriptional mechanisms, at
least in part. CONCLUSIONS: Cytokines including TNF-alpha+IFN-gamma increase
levels of endogenous BACE1, APP, and Abeta and stimulate amyloidogenic APP
processing in astrocytes. Oligomeric and fibrillar Abeta42 also increase levels
of astrocytic BACE1, APP, and beta-secretase processing. Together, our results
suggest a cytokine- and Abeta42-driven feed-forward mechanism that promotes
astrocytic Abeta production. Given that astrocytes greatly outnumber neurons,
activated astrocytes may represent significant sources of Abeta during
neuroinflammation in AD.
PMID- 22047172
TI - Social cues at encoding affect memory in 4-month-old infants.
AB - Available evidence suggests that infants use adults' social cues for learning by
the second half of the first year of life. However, little is known about the
short-term or long-term effects of joint attention interactions on learning and
memory in younger infants. In the present study, 4-month-old infants were
familiarized with visually presented objects in either of two conditions that
differed in the degree of joint attention (high vs. low). Brain activity in
response to familiar and novel objects was assessed immediately after the
familiarization phase (immediate recognition), and following a 1-week delay
(delayed recognition). The latency of the Nc component differentiated between
recognition of old versus new objects. Pb amplitude and latency were affected by
joint attention in delayed recognition. Moreover, the frequency of infant gaze to
the experimenter during familiarization differed between the two experimental
groups and modulated the Pb response. Results show that joint attention affects
the mechanisms of long-term retention in 4-month-old infants. We conclude that
joint attention helps children at this young age to recognize the relevance of
learned items.
PMID- 22047174
TI - Analysis of natural variation of the potato tuber proteome reveals novel
candidate genes for tuber bruising.
AB - Potato (Solanum tuberosum) presents a challenging organism for the genetic and
molecular dissection of complex traits due to its tetraploidy and high
heterozygosity. One such complex trait of high agronomic interest is the tuber
susceptibility to bruising upon mechanical impact, which involves an enzymatic
browning reaction. We have compared the tuber proteome of two groups of 10 potato
cultivars differing in bruising susceptibility to (i) identify de novo proteins
that contribute to bruising, based on differential protein expression, and (ii)
validate these proteins by combining proteomics with association genetics. The
comparison of 20 potato varieties yields insight into the high natural variation
of tuber protein patterns due to genetic background. Seven genes or gene families
were found that were both differentially expressed on the protein level between
groups and for which DNA polymorphisms were associated with the investigated
traits. A putative class III lipase was identified as a novel factor contributing
to the natural variation of bruising. Additionally, tuber proteome changes
triggered by mechanical impact, within and between groups, were monitored over
time. Differentially expressed proteins were found, notably lipases, patatins,
and annexins, showing remarkable time-dependent protein variation.
PMID- 22047173
TI - Variations of insecticide residual bio-efficacy on different types of walls:
results from a community-based trial in south Cameroon.
AB - BACKGROUND: Determination of residual activity of insecticides is essential
information for the selection of appropriate indoor spraying operation. The
present study was undertaken to evaluate the residual effect of three candidate
insecticide formulations on different indoor surfaces in order to guide future
interventions, in the context of Cameroon and other African countries. METHODS:
The study was conducted in the Ntougou neighbourhood in Yaounde (capital city of
Cameroon). Bendiocarb WP, lambda-cyhalothrin CS and deltamethrin WG were sprayed
on the indoor wall surfaces of local cement, wood and mud houses. Their effects
on the knockdown and mortality of the Kisumu susceptible strain of Anopheles
gambiae s.s were assessed each month from March to September 2009, using the WHO
plastic cones test. Knockdown and mortality rates were compared between different
surfaces using Chi-square test. A Kaplan-Meir model was used to estimate the time
of treatment failure. RESULTS: With bendiocarb WP, the knockdown rates were
frequently above 98% during 13 weeks after spraying, except on mud walls where it
significantly decreased at the 13th week (P < 0.05). With lambda cyhalothrin CS,
the knockdown rates remained 100% on wood surfaces during the 26 weeks trial.
However, it significantly decreased on concrete and mud surfaces from the 11th
(83%) and the 20th (88%) weeks respectively (P < 0.05). With deltamethrin WG, it
remained high on concrete surfaces during 26 weeks (> 98%); while it varied
between 60 and 100% on wood or mud surfaces. The survival estimates of bendiocarb
WP treatments remaining effective in killing An. gambiae s.s. (mortality rate >=
80%) was > 13 weeks on cement and wood surfaces and 13 weeks on mud surfaces.
Those of lambda-cyhalothrin CS were > 26 weeks on wood surfaces, and 20 weeks on
concrete and mud surfaces. By contrast, those of deltamethrin WG were 26 weeks on
concrete, 20 weeks on mud surfaces and 15 weeks on wood surfaces. CONCLUSION:
Current data suggest variable durations of spray cycles for each product,
according to the type of wall surfaces, highlighting the importance of testing
candidate products in local context before using them in large scale.
PMID- 22047175
TI - Practical considerations to guide development of access controls and decision
support for genetic information in electronic medical records.
AB - BACKGROUND: Genetic testing is increasingly used as a tool throughout the health
care system. In 2011 the number of clinically available genetic tests is
approaching 2,000, and wide variation exists between these tests in their
sensitivity, specificity, and clinical implications, as well as the potential for
discrimination based on the results. DISCUSSION: As health care systems
increasingly implement electronic medical record systems (EMRs) they must
carefully consider how to use information from this wide spectrum of genetic
tests, with whom to share information, and how to provide decision support for
clinicians to properly interpret the information. Although some characteristics
of genetic tests overlap with other medical test results, there are reasons to
make genetic test results widely available to health care providers and
counterbalancing reasons to restrict access to these test results to honor
patient preferences, and avoid distracting or confusing clinicians with
irrelevant but complex information. Electronic medical records can facilitate and
provide reasonable restrictions on access to genetic test results and deliver
education and decision support tools to guide appropriate interpretation and use.
SUMMARY: This paper will serve to review some of the key characteristics of
genetic tests as they relate to design of access control and decision support of
genetic test information in the EMR, emphasizing the clear need for health
information technology (HIT) to be part of optimal implementation of genetic
medicine, and the importance of understanding key characteristics of genetic
tests when designing HIT applications.
PMID- 22047176
TI - Ultrafast dynamics of isolated fluorenone.
AB - The ultrafast dynamics of isolated 9-fluorenone was studied by femtosecond time
resolved photoionization and photoelectron spectroscopy. The molecule was excited
around 264-266 nm into the S(6) state. The experimental results indicate that the
excitation is followed by a multistep deactivation. A time constant of 50 fs or
less corresponds to a fast redistribution of energy within the initially excited
manifold of states, i.e., a motion away from the Franck-Condon region. Internal
conversion to the S(1) state then proceeds within 0.4 ps. The S(1) state is long
lived, and only a lower bound of 20 ps can be derived. In addition, we computed
excited state energies and oscillator strengths by TD-DFT theory, supporting the
interpretation of the experimental data.
PMID- 22047177
TI - Preparation of single-stranded DNA from PCR products with streptavidin magnetic
beads.
AB - The preparation of single-stranded DNA from double-stranded PCR products is an
essential step in the identification of aptamers by Systematic Evolution of
Ligands by EXponential enrichment (SELEX). The most widely used method for
producing single-stranded DNA is alkaline denaturation of biotinylated PCR
products attached to streptavidin-coated magnetic beads. Recently, it has been
suggested that this method may be unsuitable due to the release of interfering
amounts of streptavidin and biotinylated DNA. In this article, the alkaline
method is compared with a thermal method that is known to release significant
amounts of streptavidin and biotinylated DNA. Results show that trace amounts of
streptavidin and biotinylated DNA are released in the alkaline method, but this
can be curtailed by preconditioning the beads in aqueous sodium hydroxide. The
main product in the alkaline method is single-stranded DNA, which is produced in
high yield.
PMID- 22047178
TI - Improvement of tetracaine antinociceptive effect by inclusion in cyclodextrins.
AB - Local anesthetics (LA) are among the most important pharmacological compounds
used to attenuate or eliminate pain. However, systemic toxicity is still a
limitation for LA application, especially for ester-type drugs, such as
tetracaine (TTC) that presents poor chemical stability (due to hydrolysis by
plasma esterases). Several approaches have been used to improve LA pharmaceutical
properties, including the employment of drug-delivery systems. Here we used beta
cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to develop
two new TTC formulations (TTC:beta-CD and TTC:HP-beta-CD). The inclusion
complexes formation, in a 1:1 stoichiometry, was confirmed by differential
scanning calorimetry, X-ray diffraction, UV-VIS absorption and fluorescence.
Nuclear magnetic resonance (DOSY experiments) revealed that TTC association with
HP-beta-CD is stronger (Ka=1200 mol/L(-1)) than with beta-CD (Ka=845 mol/L(-1)).
Moreover, nuclear Overhauser effect (NOE) experiments provided information on the
topology of the complexes, where TTC aromatic ring is buried inside the CD
hydrophobic cavity. In vitro tests with 3T3 fibroblast cells culture revealed
that complexation decreased TTC cytotoxicity. In addition, the total analgesic
effect of TTC, tested in rats through the infraorbital nerve test, was improved
in 36% with TTC:beta-CD and TTC:HP-beta-CD. In conclusion, these formulations
presented potential for future clinical use, by reducing the toxicity and
increasing the antinociceptive effect of tetracaine.
PMID- 22047181
TI - Experiences of female survivors of sexual violence in eastern Democratic Republic
of the Congo: a mixed-methods study.
AB - BACKGROUND: The conflict in eastern Democratic Republic of the Congo (DRC) is the
deadliest since World War II. Over a decade of fighting amongst an array of armed
groups has resulted in extensive human rights abuses, particularly the widespread
use of sexual violence against women. METHODS: Using a mixed-methods approach, we
surveyed a non-random sample of 255 women attending a referral hospital and two
local non-governmental organizations to characterize their experiences of sexual
and gender-based violence (SGBV). We then conducted focus groups of 48 women
survivors of SGBV to elaborate on survey findings. Quantitative and qualitative
data underwent thematic and statistical analysis respectively. FINDINGS: Of the
women surveyed, 193 (75.7%) experienced rape. Twenty-nine percent of raped women
were rejected by their families and 6% by their communities. Thirteen percent of
women had a child from rape. Widowhood, husband abandonment, gang rape, and
having a child from rape were significant risk factors for social rejection.
Mixed methods findings show rape survivors were seen as "contaminated" with HIV,
contributing to their isolation and over 95% could not access prophylactic care
in time. Receiving support from their husbands after rape was protective against
survivors' feelings of shame and social isolation. INTERPRETATION: Rape results
not only in physical and psychological trauma, but can destroy family and
community structures. Women face significant obstacles in seeking services after
rape. Interventions offering long-term solutions for hyper-vulnerable women are
vital, but lacking; reintegration programs on SGBV for women, men, and
communities are also needed.
PMID- 22047179
TI - Metal selectivity of the Escherichia coli nickel metallochaperone, SlyD.
AB - SlyD is a Ni(II)-binding protein that contributes to nickel homeostasis in
Escherichia coli. The C-terminal domain of SlyD contains a rich variety of metal
binding amino acids, suggesting broader metal binding capabilities, and previous
work demonstrated that the protein can coordinate several types of first-row
transition metals. However, the binding of SlyD to metals other than Ni(II) has
not been previously characterized. To improve our understanding of the in vitro
metal-binding activity of SlyD and how it correlates with the in vivo function of
this protein, the interactions between SlyD and the series of biologically
relevant transition metals [Mn(II), Fe(II), Co(II), Cu(I), and Zn(II)] were
examined by using a combination of optical spectroscopy and mass spectrometry.
Binding of SlyD to Mn(II) or Fe(II) ions was not detected, but the protein
coordinates multiple ions of Co(II), Zn(II), and Cu(I) with appreciable affinity
(K(D) values in or below the nanomolar range), highlighting the promiscuous
nature of this protein. The order of affinities of SlyD for the metals examined
is as follows: Mn(II) and Fe(II) < Co(II) < Ni(II) ~ Zn(II) ? Cu(I). Although the
purified protein is unable to overcome the large thermodynamic preference for
Cu(I) and exclude Zn(II) chelation in the presence of Ni(II), in vivo studies
reveal a Ni(II)-specific function for the protein. Furthermore, these latter
experiments support a specific role for SlyD as a [NiFe]-hydrogenase enzyme
maturation factor. The implications of the divergence between the metal
selectivity of SlyD in vitro and the specific activity in vivo are discussed.
PMID- 22047180
TI - Transcript and metabolite analysis in Trincadeira cultivar reveals novel
information regarding the dynamics of grape ripening.
AB - BACKGROUND: Grapes (Vitis vinifera L.) are economically the most important fruit
crop worldwide. However, the complexity of molecular and biochemical events that
lead to the onset of ripening of nonclimacteric fruits is not fully understood
which is further complicated in grapes due to seasonal and cultivar specific
variation. The Portuguese wine variety Trincadeira gives rise to high quality
wines but presents extremely irregular berry ripening among seasons probably due
to high susceptibility to abiotic and biotic stresses. RESULTS: Ripening of
Trincadeira grapes was studied taking into account the transcriptional and
metabolic profilings complemented with biochemical data. The mRNA expression
profiles of four time points spanning developmental stages from pea size green
berries, through veraison and mature berries (EL 32, EL 34, EL 35 and EL 36) and
in two seasons (2007 and 2008) were compared using the Affymetrix GrapeGen(r)
genome array containing 23096 probesets corresponding to 18726 unique sequences.
Over 50% of these probesets were significantly differentially expressed (1.5
fold) between at least two developmental stages. A common set of modulated
transcripts corresponding to 5877 unigenes indicates the activation of common
pathways between years despite the irregular development of Trincadeira grapes.
These unigenes were assigned to the functional categories of "metabolism",
"development", "cellular process", "diverse/miscellanenous functions",
"regulation overview", "response to stimulus, stress", "signaling", "transport
overview", "xenoprotein, transposable element" and "unknown". Quantitative RT-PCR
validated microarrays results being carried out for eight selected genes and five
developmental stages (EL 32, EL 34, EL 35, EL 36 and EL 38). Metabolic profiling
using 1H NMR spectroscopy associated to two-dimensional techniques showed the
importance of metabolites related to oxidative stress response, amino acid and
sugar metabolism as well as secondary metabolism. These results were integrated
with transcriptional profiling obtained using genome array to provide new
information regarding the network of events leading to grape ripening.
CONCLUSIONS: Altogether the data obtained provides the most extensive survey
obtained so far for gene expression and metabolites accumulated during grape
ripening. Moreover, it highlighted information obtained in a poorly known variety
exhibiting particular characteristics that may be cultivar specific or dependent
upon climatic conditions. Several genes were identified that had not been
previously reported in the context of grape ripening namely genes involved in
carbohydrate and amino acid metabolisms as well as in growth regulators;
metabolism, epigenetic factors and signaling pathways. Some of these genes were
annotated as receptors, transcription factors, and kinases and constitute good
candidates for functional analysis in order to establish a model for ripening
control of a non-climacteric fruit.
PMID- 22047182
TI - Transcriptome analysis of Bupleurum chinense focusing on genes involved in the
biosynthesis of saikosaponins.
AB - BACKGROUND: Bupleurum chinense DC. is a widely used traditional Chinese medicinal
plant. Saikosaponins are the major bioactive constituents of B. chinense, but
relatively little is known about saikosaponin biosynthesis. The 454
pyrosequencing technology provides a promising opportunity for finding novel
genes that participate in plant metabolism. Consequently, this technology may
help to identify the candidate genes involved in the saikosaponin biosynthetic
pathway. RESULTS: One-quarter of the 454 pyrosequencing runs produced a total of
195, 088 high-quality reads, with an average read length of 356 bases (NCBI SRA
accession SRA039388). A de novo assembly generated 24, 037 unique sequences (22,
748 contigs and 1, 289 singletons), 12, 649 (52.6%) of which were annotated
against three public protein databases using a basic local alignment search tool
(E-value <=1e-10). All unique sequences were compared with NCBI expressed
sequence tags (ESTs) (237) and encoding sequences (44) from the Bupleurum genus,
and with a Sanger-sequenced EST dataset (3, 111). The 23, 173 (96.4%) unique
sequences obtained in the present study represent novel Bupleurum genes. The ESTs
of genes related to saikosaponin biosynthesis were found to encode known enzymes
that catalyze the formation of the saikosaponin backbone; 246 cytochrome P450
(P450s) and 102 glycosyltransferases (GTs) unique sequences were also found in
the 454 dataset. Full length cDNAs of 7 P450s and 7 uridine diphosphate GTs
(UGTs) were verified by reverse transcriptase polymerase chain reaction or by
cloning using 5' and/or 3' rapid amplification of cDNA ends. Two P450s and three
UGTs were identified as the most likely candidates involved in saikosaponin
biosynthesis. This finding was based on the coordinate up-regulation of their
expression with beta-AS in methyl jasmonate-treated adventitious roots and on
their similar expression patterns with beta-AS in various B. chinense tissues.
CONCLUSIONS: A collection of high-quality ESTs for B. chinense obtained by 454
pyrosequencing is provided here for the first time. These data should aid further
research on the functional genomics of B. chinense and other Bupleurum species.
The candidate genes for enzymes involved in saikosaponin biosynthesis, especially
the P450s and UGTs, that were revealed provide a substantial foundation for
follow-up research on the metabolism and regulation of the saikosaponins.
PMID- 22047183
TI - Hippocampal integrity and neurocognition in first-episode schizophrenia: a
multidimensional study.
AB - OBJECTIVES: Impairments in memory and executive function are key components of
schizophrenia. These disturbances have been linked to several subcortical and
cortical networks. For example, anatomical and functional changes in the
hippocampus have been linked to deficits in these cognitive domains. However, the
association between hippocampal morphometry, neurochemistry and function is
controversial. Therefore, we aimed to investigate the relationship between
hippocampal anomalies and their functional relevance. METHODS: Fifty-seven first
episode schizophrenia patients (FE-SZ) and 61 healthy control subjects (HC)
participated in this study. Hippocampal volumes were investigated using
structural magnetic resonance imaging (sMRI) and hippocampal neurochemistry was
determined using proton magnetic resonance spectroscopy (1H MRS). Verbal memory
was used as a hippocampus-dependent cognitive task whereas working memory and
cognitive flexibility assessed frontal lobe function. RESULTS: FE-SZ presented
smaller volumes of the left hippocampus, with a significant correlation between
left hippocampal volume and verbal memory performance (immediate recall). There
was also an inverse correlation between neurochemical ratios (NAA/Cho and Cho/Cr)
and verbal memory (delayed recognition). Tests of cognitive flexibility and
working memory were not correlated with MRI and 1H MRS values. Compared to HC, FE
SZ demonstrated reduced performance in all of the assessed neurocognitive
domains. CONCLUSIONS: These results point to a relationship between verbal memory
and hippocampal integrity in schizophrenia patients which might be independent
from deficits in other memory domains. Disturbed verbal memory functions in FE-SZ
might be linked specifically to hippocampal function.
PMID- 22047184
TI - Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association
study.
AB - OBJECTIVES: Lower levels of serum brain derived neurotrophic factor (BDNF) is one
of the best known biomarkers of depression. To identify genetic variants
associated with serum BDNF, we tested the Val66Met (rs6265) functional variant
and conducted a genome-wide association scan (GWAS). METHODS: In a community
based sample (N = 2054; aged 19-101, M = 51, SD = 15) from Sardinia, Italy, we
measured serum BDNF concentration and conducted a GWAS. RESULTS: We estimated the
heritability of serum BDNF to be 0.48 from sib-pairs. There was no association
between serum BDNF and Val66Met in the SardiNIA sample and in a meta-analysis of
published studies (k = 13 studies, total n = 4727, P = 0.92). Although no genome
wide significant associations were identified, some evidence of association was
found in the BDNF gene (rs11030102, P = 0.001) and at two loci (rs7170215, P =
4.8 * 10-5 and rs11073742 P = 1.2 * 10-5) near and within NTRK3 gene, a
neurotrophic tyrosine kinase receptor. CONCLUSIONS: Our study and meta-analysis
of the literature indicate that the BDNF Val66Met variant is not associated with
serum BDNF, but other variants in the BDNF and NTRK3 genes might regulate the
level of serum BDNF.
PMID- 22047185
TI - The antiretroviral efficacy of highly active antiretroviral therapy and plasma
nevirapine concentrations in HIV-TB co-infected Indian patients receiving
rifampicin based antituberculosis treatment.
AB - BACKGROUND: Rifampicin reduces the plasma concentrations of nevirapine in human
immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are
administered these drugs concomitantly. We conducted a prospective interventional
study to assess the efficacy of nevirapine-containing highly active
antiretroviral treatment (HAART) when co-administered with rifampicin-containing
antituberculosis treatment (ATT) and also measured plasma nevirapine
concentrations in patients receiving such a nevirapine-containing HAART regimen.
METHODS: 63 cases included antiretroviral treatment naive HIV-TB co-infected
patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing
ATT followed by nevirapine-containing HAART. In control group we included 51 HIV
patients without tuberculosis and on nevirapine-containing HAART. They were
assessed for clinical and immunological response at the end of 24 and 48 weeks.
Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of
starting HAART. RESULTS: 97 out of 114 (85.1%) patients were alive at the end of
48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3
(p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73%
patients in cases had viral loads of less than 400 copies/ml at the end of 48
weeks. The mean (+/- SD) Nevirapine concentrations of cases and control at 14,
28, 42 and 180 days were 2.19 +/- 1.49 vs. 3.27 +/- 4.95 (p = 0.10), 2.78 +/-
1.60 vs. 3.67 +/- 3.59 (p = 0.08), 3.06 +/- 3.32 vs. 4.04 +/- 2.55 (p = 0.10)
respectively and 3.04 MUg/ml (in cases). CONCLUSIONS: Good immunological and
clinical response can be obtained in HIV-TB co-infected patients receiving
rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough
concentrations. This suggests that rifampicin-containing ATT may be co
administered in resource limited setting with nevirapine-containing HAART regimen
without substantial reduction in antiretroviral effectiveness. Larger sample
sized studies and longer follow-up are required to identify populations of
individuals where the reduction in nevirapine concentration may result in lower
ART response or shorter response duration.
PMID- 22047186
TI - Bioassay-directed identification of novel antiandrogenic compounds in bile of
fish exposed to wastewater effluents.
AB - The widespread occurrence of feminized male fish downstream of some UK Wastewater
Treatment Works (WwTWs) has been associated with exposure to estrogenic and
potentially antiandrogenic (AA) contaminants in the effluents. In this study,
profiling of AA contaminants in WwTW effluents and fish was conducted using HPLC
in combination with in vitro androgen receptor transcription screens. Analysis of
extracts of wastewater effluents revealed complex profiles of AA activity
comprising 21-53 HPLC fractions. Structures of bioavailable antiandrogens were
identified by exposing rainbow trout to a WwTW effluent and profiling the bile
for AA activity using yeast (anti-YAS) and mammalian-based (AR-CALUX) androgen
receptor transcription screens. The predominant fractions with AA activity in
both androgen receptor screens contained the germicides chlorophene and
triclosan, and together these contaminants accounted for 51% of the total anti
YAS activity in the fish bile. Other AA compounds identified in bile included
chloroxylenol, dichlorophene, resin acids, napthols, oxybenzone, 4-nonylphenol,
and bisphenol A. Pure standards of these compounds were active in the androgen
receptor screens at potencies relative to flutamide of between 0.1 and 13.0.
Thus, we have identified, for the first time, a diverse range of AA chemicals in
WwTWs that are bioavailable to fish and which need to be assessed for their risk
to the reproductive health of these organisms and other aquatic biota.
PMID- 22047187
TI - Long-term outcome of laparoscopic Nissen procedure in pediatric patients with
gastroesophageal reflux disease measured using the modified QPSG Roma III
European Society for Pediatric Gastroenterology Hepatology and Nutrition's
questionnaire.
AB - BACKGROUND/PURPOSE: Laparoscopic fundoplication (LF) represents the gold standard
for surgical treatment for pediatric patients with gastroesophageal reflux
disease (GERD). METHODS: We report the results of long-term outcome of 36
patients who had undergone LF from January to December 1998, with a follow-up
longer than 10 years (range, 11-12 years). The patients were invited, by phone,
to undergo a clinical follow-up. All patients underwent the modified European
Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)'s Roma
III questionnaire; however, only 22 out of 36 patients accepted to be controlled
in a day hospital setting, and 10 out of 36 accepted to undergo a telephonic
questionnaire. Our study is focused on the data of these 32 patients. RESULTS:
Twenty-eight out of 32 (87.5%) patients had completely recovered; 4 out of 32
patients (12.5%) had a mild persistent GER; 9 out of 32 patients (28%) referred a
mild dysphagia; 21 out of 32 (66%) patients could burp; and only 9 out of 32
(28%) patients could vomit. The cosmetic result was good in 30 out of 32 (94%)
patients. The weight/height ratio was satisfactory in 28 out of 32 (87.5%)
patients. The quality of life was good in 28 out of 32 (87.5%) patients.
CONCLUSIONS: Our experience shows that the long-term follow-up after LF produces
a good clinical result and a good quality of life. The modified ESPGHAN's Roma
III questionnaire seems an effective way to check the long-term results, because
it avoids submitting patients to long and not well tolerated instrumental exams.
PMID- 22047188
TI - Tight and uniform layer of covalently bound aminoethylophenyl groups
perpendicular to gold surface for attachment of biomolecules.
AB - Strongly adhered layers of the compound with the primary amino group directed
toward the solution were obtained at the gold surface by chronoamperometric
electroreduction of 4-aminoethylobenzenodiazonium salt (AEBD) in acetonitrile
solution at appropriately selected potential. The used techniques (EQCM, AFM,
EIS, PM, IRRAS) showed that the nature and thickness of formed aminoethylophenyl
layer strongly depend on the potential applied to the electrode. Electroreduction
of AEBD salt at a potential more negative than -0.6 V (vs Ag/AgCl) leads to about
monolayer on the gold surface. Additionally, such a layer was very tight and
uniform. The electrochemical measurements indicate that the efficient and precise
attachment of biomolecules to the aminoethylophenyl layer is only possible when
this layer is formed at appropriate potential. This was shown for ss- and dsDNA.
PMID- 22047189
TI - Erratum.
PMID- 22047191
TI - Antimicrobial flavonoids from Tridax procumbens.
AB - Callus culture of Tridax procumbens has been established on Murashige and Skoog's
medium supplemented with NAA and BAP from nodal segments. Free and bound
flavonoids were extracted from 2, 4, 6 and 8 weeks old calli by a well
established method. These free flavonoids were then screened against
Staphylococcus aureus (bacteria) and Candida albicans (yeast) for their
antimicrobial potential. Minimum inhibitory concentration, minimum
bactericidal/fungicidal concentrations and total activity were also evaluated.
Apigenin, quercetin and kaempferol were identified from free flavonoids of 4
weeks old callus (most active) through, thin layer chromatography, (TLC)
preparative TLC, MP and IR spectral studies.
PMID- 22047192
TI - Rh-catalyzed ortho-selective C-H borylation of N-functionalized arenes with
silica-supported bridgehead monophosphine ligands.
AB - Supported phosphine-Rh systems, prepared in situ from silica-supported bridgehead
monophosphines and [Rh(OH)(cod)](2), have enabled ortho-selective C-H borylation
for a range of arenes containing nitrogen-based directing groups. The
regioselectivity was excellent with various N-directing groups, including
saturated and unsaturated N-heterocycles, tert-aminoalkyl groups, and imine-type
C-N double bonds. The reaction showed significant tolerance toward steric
repulsion around the reacting C-H bond. This Rh catalysis complements the Ir
catalyzed ortho-borylation, which is effective for arenes with oxygen-based
directing groups.
PMID- 22047193
TI - Malaria with neurological involvement in Ugandan children: effect on cognitive
ability, academic achievement and behaviour.
AB - BACKGROUND: Malaria is a leading cause of ill health and neuro-disability in
children in sub-Saharan Africa. Impaired cognition is a common outcome of malaria
with neurological involvement. There is also a possibility that academic
achievement may be affected by malaria with neurological involvement given the
association between cognitive ability and academic achievement. This study
investigated the effect of malaria with neurological involvement on cognitive
ability, behaviour and academic achievement. METHODS: This prospective case
control study was carried out in Kampala City, Uganda between February 2008 and
October 2010. Sixty-two children with a history of malaria with neurological
involvement were followed up and given assessments for cognitive ability (working
memory, reasoning, learning, visual spatial skills and attention), behaviour
(internalizing and externalizing problems) and academic achievement (arithmetic,
spelling and reading) three months after the illness. Sixty-one community
controls recruited from the homes or neighbouring families of the cases were also
given the same assessments. Tests scores of the two groups were compared using
analysis of covariance with age, sex, level of education, nutritional status and
quality of the home environment as covariates. This study was approved by the
relevant ethical bodies and informed consent sought from the caregivers. RESULTS:
Children in the malaria group had more behavioural problems than the community
controls for internalizing problems (estimated mean difference = -3.71, 95%
confidence interval (CI), = -6.34 to -1.08, p = 0.007). There was marginal
evidence of lower attention scores (0.40, CI = -0.05 to 0.86, p = 0.09). However,
excluding one child from the analyses who was unable to perform the tests
affected the attention scores to borderline significance (0.32, CI, = 0.01 to
0.62, p = 0.05). No significant differences were observed in other cognitive
abilities or in academic achievement scores. CONCLUSION: Malaria with
neurological involvement affects behaviour, with a minimal effect on attention
but no detectable effect on academic achievement at three months post discharge.
This study provides evidence that development of cognitive deficits after malaria
with neurological involvement could be gradual with less effect observed in the
short term compared to the long term.
PMID- 22047194
TI - Prospective memory deficits in Ecstasy users: effects of longer ongoing task
delay interval.
AB - Ecstasy use has been associated with neurotoxicity and neurocognitive impairment
in a variety of domains, including prospective memory (ProM), which involves the
delayed execution of a previously encoded intention in response to a specific
cue. The present study adopted the multiprocess theory of ProM to evaluate the
hypothesis that Ecstasy users would evidence differentially impaired ProM on
longer versus shorter ongoing task delays. Ecstasy (n = 31) users, high-risk
alcohol users (n = 21), and healthy nonusers (n = 31) completed the short (2-min)
and long (15-min) delay ProM scales of the Memory for Intentions Screening Test.
Results showed a significant group by ProM delay interaction, such that Ecstasy
users performed comparably to the comparison groups on short-delay trials, but
were impaired on long-delay ProM, particularly for time-based cues. Among the
Ecstasy users, long-delay ProM was positively associated with risky decision
making, but not with retrospective memory or other aspects of executive
functions. These findings suggest that Ecstasy users may be particularly
susceptible to deficits in strategic target monitoring and maintenance of cue
intention pairings over longer ProM delays. Findings are discussed in the context
of their potential everyday functioning (e.g., academic, vocational) and
treatment implications for Ecstasy users.
PMID- 22047195
TI - Principles of statistics in surgery.
AB - Surgery, like any other scientific discipline, requires a systematic analysis of
all its different variables in order to prove the real significance of research
findings. Statistics, the science of numerical evaluation, can thoroughly help to
determine the real value of surgical treatment. In this work, we study the
statistical tests and principles needed to demonstrate their role in surgical
research. Without a strong statistical background, a researcher may feel
overwhelmed when deciding what statistical methods to utilize in research.
Determining what type of data to collect and what hypothesis test to run can
alter the entire way a surgical study is conducted. The relationship between
power, sample size and effect size is discussed as well as the components
necessary for a power analysis. Selecting an appropriate sample size is of utmost
importance in any type of research since an undersized sample can invalidate an
entire study. Categorical surgical data, numerical data, and the appropriate
statistical procedures needed for analysis are reviewed. Methods discussed
include the 2-Sample t-test, Mann Whitney U test, Kruskal-Wallis, ANOVA, Chi
Square test and Fisher's exact test.
PMID- 22047196
TI - Advanced imaging technology in surgical innovation.
AB - Advanced imaging technologies including computed tomography (CT) and magnetic
resonance imaging (MRI) have immensely expanded possibilities in imaging and
surgery. The accurate visualization of bones and soft tissue has transformed the
surgical management of numerous diseases, including middle ear disease,
orthopedic and reconstructive cases, and cancer. In fact, in surgical
subspecialties such as neurosurgery, CT and MRI are the diagnostic modalities of
choice for preoperative evaluation of patients. Furthermore, the ongoing
development of the newer imaging technologies continues to expand image-guided
surgical treatments. The development of new radiological modalities combined with
the modern training of surgeons will provide an exciting landscape for future
practicing physicians.
PMID- 22047197
TI - Magnesium sulfate does not protect spinal cord against ischemic injury.
AB - OBJECTIVE: We tested various doses of MgSO(4) to investigate the effect of Mg on
a spinal cord ischemia. METHODS: Rats were treated with either MgSO(4) (30, 100,
or 300 mg/kg; group Mg(low), group Mg(medium), group Mg(high), respectively, n =
10 for each) or saline (control group; n = 10) before ischemia. Spinal cord
ischemia was induced using a balloon-tipped catheter placed on proximal
descending aorta. During surgery, hemodynamic variables were recorded before
ischemia, during aortic occlusion and after reperfusion. Neurologic function was
assessed using the motor deficit index (MDI; 0 = normal, 6 = complete paralysis)
until seven days after reperfusion, and histologic examination of spinal cord was
performed. RESULTS: After reperfusion, the mean arterial pressure in the group
Mg(high) was significantly lower than other groups. Compared to the control
group, the groups Mg(low) and Mg(medium) did not show any difference in MDI and
the group Mg(high) showed significantly higher MDI. The number of normal motor
neurons was similar among other groups except the group Mg(high) had a
significantly fewer normal motor neurons. CONCLUSIONS: Intravenous MgSO(4) with
low or medium dose (30, or 100 mg/kg) did not improve neurological injury
following spinal cord ischemia. Furthermore, higher dose of MgSO(4) (300 mg/kg)
resulted in hemodynamic instability and aggravated neurologic outcome.
PMID- 22047198
TI - Platelet-rich plasma application and heterotopic bone formation following total
hip arthroplasty.
AB - Activated blood platelets play a critical, early role in the wound healing
response by releasing several types of growth factors at the site of injury which
mediate the initial stages of tissue repair. Autologously derived platelet-rich
plasma has been applied during surgery as a healing aid and some studies have
shown benefit with total joint arthroplasty procedures such as in the knee.
However, little has been published regarding the use of platelet-rich plasma
during total hip arthroplasty. The hip is especially prone to develop islands of
heterotopic bone following arthroplasty which can lead to pain, limited motion,
and even ankylosis of the joint. If this condition is exacerbated by platelet
rich plasma, this could present a barrier to the use of this adjuvant in total
hip arthroplasty. This retrospective, controlled clinical study examined the
effect of platelet rich plasma application during closure following total hip
arthroplasty on heterotopic ossification. By one year, 21.3% of the control
patients developed heterotopic bone (91 patients, 94 hips, Brooker grades I-III)
compared to 12.9% of the treatment patients (76 patients, 85 hips, Brooker grades
I-II). These differences were not significant (p = 0.478, power = 0.90). Thus,
the use of platelet-rich plasma in this procedure does not appear to influence
the incidence or severity of heterotopic ossification which should help to
justify further clinical research to more fully understand whether this
autologous blood product has a role in total hip arthroplasty.
PMID- 22047199
TI - Two-day fasting prior to intestinal ischemia-reperfusion injury on bacterial
translocation in rats.
AB - PURPOSE: The aim of this study is to verify the effect of two-day fasting prior
to intestinal ischemia-reperfusion (I/R) injury on bacterial translocation (BT).
MATERIALS AND METHODS: Mail Sprague-Dawley rats were divided into four groups:
group 1, control rats that underwent sham operation only; group 2, rats fasted
for two days prior to sham operation; group 3, rats that underwent occlusion of
mesenteric vessels for 30 min followed by reperfusion for 4 hr; and group 4, rats
fasted for two days prior to the same intestinal I/R injury as in group 3. In all
groups, E. coli labeled with (99m)Tc were inoculated into the terminal ileum. Two
hr after inoculation of E. coli, the rats were killed. A segment of ileum was
obtained for histological examination and samples of mesenteric lymph nodes
(MLNs), liver, lung, blood, and spleen were obtained for radioactivity
determination. RESULTS: There were no significant differences in the intestinal
mucosa and radioactivity of all samples between groups 1 and 2. Group 3 showed
significantly shorter mucosa and villi, and higher radioactivity of samples,
except for MLNs, compared to group 1. Group 4 showed similar mucosa and villi,
but significantly higher radioactivity of samples, except for MLNs, compared to
group 3. CONCLUSION: Two-day fasting without I/R injury does not cause mucosal
change and BT, but in cases following intestinal I/R injury, two-day fasting
increases the susceptibility of BT to systemic organs in rats.
PMID- 22047200
TI - Type of steatosis influences microcirculation and fibrogenesis in different rat
strains.
AB - This study investigates the impact of rat strain on the development of
nonalcoholic fatty liver disease (NAFLD) focusing on morphological features and
microcirculation. Male rats of Lewis, Wistar, and Sprague Dawley (n = 6 per
strain and group) were randomized into a high-fat group which was fed with a
special high-fat nutrition for a 3-week period and a control group which received
standard nutrition. Intravital microscopy was used for the evaluation of
microcirculation and correlated to morphological changes using a fatty liver
scoring system. All three strains receiving a high-fat diet developed a grade 3
steatosis (>66% liver cell steatosis). Whereas Lewis showed a solely
microvesicular steatosis, Wistar developed a mixed form and Sprague Dawley showed
a pure macrovesicular steatosis and the highest degree of fibrosis and hepatocyte
damage. Microcirculatory results revealed that sinusoidal density was already
affected by a microvesicular steatosis and decreased with increasing
macrovesicular proportion (Lewis: 18%, Wistar: 31%, Sprague Dawley: 23%). The
degree of steatosis correlates with reduced blood flow velocity in central veins
as well as in sinusoids (Lewis: 28%, Wistar: 39%, Sprague Dawley 44%). The
densities of hepatocytes and hepatic stellate cells were only impaired once
macrovesicular cell steatosis (Wistar and Sprague Dawley) was present. The
development of NAFLD in the rat revealed strain-specific morphological features
correlating with microcirculatory changes that should be considered in further
studies using these models.
PMID- 22047201
TI - The effects of testosterone on intestinal ischemia/reperfusion in rats.
AB - ABSTRACT Ischemic injury to the gut is believed to occur in many serious
clinical conditions. Our aim was to investigate the postischemia/reperfusion
(I/R) effects of exogenously administered testosterone on the intestines of
normal and orchiectomized rats.Forty-eight rats were divided into eight groups of
six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone
treated group; (3) I/R group: Rats were subjected to the surgical procedures and
underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4)
I/R + testosterone-treated group: Rats were subjected to the surgical procedures
and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats
were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy
group: Rats were subjected to the surgical procedures as well as orchiectomy; (7)
orchiectomy + testosterone-treated group: Rats were subjected to the surgical
procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and
(8) I/R + orchiectomy + testosterone-treated group. The histological findings of
this study paralleled the observed degree of lipid peroxidation (LPO) and protein
oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy,
and I/R + orchiectomy + testosterone groups, but was less in the I/R +
testosterone group. Histopathological injury also paralleled the degree of
oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R +
orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of
testosterone in the presence of testes significantly protected intestinal tissue
against I/R mucosal injuries, while administration of testosterone in the absence
of testes did not significantly protect intestinal tissue against I/R mucosal
injuries.
PMID- 22047202
TI - Comparison of long-term biocompability of PVDF and PP meshes.
AB - BACKGROUND: Abdominal hernia repair is the most frequently performed operation in
surgery. Mesh repair in hernia surgery has become an integral component. Although
meshes made of PVDF are already in clinical use, so far no data of long-term
biocompability are available. METHODS: In this study a PVDF mesh was compared to
a polypropylene mesh with regard to its long-term biocompatibility. A total of 28
rats were randomized to two groups. Mesh material was implanted subcutaneously;
animals were euthanized seven days and six months postoperatively. The quantity
of inflammatory tissue response was characterized by measuring the diameter of
the foreign body granuloma. Furthermore quality of cellular immune response (T
lymphocytes, macrophages, and neutrophils), and inflammation (COX-2) was analyzed
by immunohistochemistry. Furthermore the collagen type I/III ratio was
determined. RESULTS: Macrophages, T-lymphocytes, neutrophiles, and COX-2 declined
significantly up to six months postoperatively in comparison to day 7 for both
PVDF and PP meshes, and in both groups the collagen ratio increased significantly
in the course of time. PVDF meshes showed a foreign body granuloma size
significantly reduced compared to PP (7 days: 20 +/- 2 MUm vs. 27 +/- 2 MUm; 6
months 15 +/- 2 MUm vs. 22 +/- 3 MUm; p < .001). However no significant
differences were found analyzing cellular response six months postoperatively.
CONCLUSIONS: Our current data suggest that even in the long-term course after six
months and despite a higher effective surface of the PVDF samples it showed a
smaller foreign body granuloma than with PP whereas the cellular response was
similar.
PMID- 22047203
TI - Collagen implants in hernia repair.
PMID- 22047206
TI - Shotgun proteomic analysis of long-distance drought signaling in rice roots.
AB - Rice (Oryza sativa L. cv. IR64) was grown in split-root systems to analyze long
distance drought signaling within root systems. This in turn underpins how root
systems in heterogeneous soils adapt to drought. The approach was to compare four
root tissues: (1) fully watered; (2) fully droughted and split-root systems where
(3) one-half was watered and (4) the other half was droughted. This was
specifically aimed at identifying how droughted root tissues altered the proteome
of adjacent wet roots by hormone signals and how wet roots reciprocally affected
dry roots hydraulically. Quantitative label-free shotgun proteomic analysis of
four different root tissues resulted in identification of 1487 nonredundant
proteins, with nearly 900 proteins present in triplicate in each treatment.
Drought caused surprising changes in expression, most notably in partially
droughted roots where 38% of proteins were altered in level compared to adjacent
watered roots. Specific functional groups changed consistently in drought.
Pathogenesis-related proteins were generally up-regulated in response to drought
and heat-shock proteins were totally absent in roots of fully watered plants.
Proteins involved in transport and oxidation-reduction reactions were also highly
dependent upon drought signals, with the former largely absent in roots receiving
a drought signal while oxidation-reduction proteins were strongly present during
drought. Finally, two functionally contrasting protein families were compared to
validate our approach, showing that nine tubulins were strongly reduced in
droughted roots while six chitinases were up-regulated, even when the signal
arrived remotely from adjacent droughted roots.
PMID- 22047207
TI - Dispersal state of multiwalled carbon nanotubes elicits profibrogenic cellular
responses that correlate with fibrogenesis biomarkers and fibrosis in the murine
lung.
AB - We developed a dispersal method for multiwalled carbon nanotubes (MWCNTs) that
allows quantitative assessment of dispersion on profibrogenic responses in tissue
culture cells and in mouse lung. We demonstrate that the dispersal of as-prepared
(AP), purified (PD), and carboxylated (COOH) MWCNTs by bovine serum albumin (BSA)
and dipalmitoylphosphatidylcholine (DPPC) influences TGF-beta1, PDGF-AA, and IL
1beta production in vitro and in vivo. These biomarkers were chosen based on
their synergy in promoting fibrogenesis and cellular communication in the
epithelial-mesenchymal cell trophic unit in the lung. The effect of dispersal was
most noticeable in AP- and PD-MWCNTs, which are more hydrophobic and unstable in
aqueous buffers than hydrophilic COOH-MWCNTs. Well-dispersed AP- and PD-MWCNTs
were readily taken up by BEAS-2B, THP-1 cells, and alveolar macrophages (AM) and
induced more prominent TGF-beta1 and IL-1beta production in vitro and TGF-beta1,
IL-1beta, and PDGF-AA production in vivo than nondispersed tubes. Moreover, there
was good agreement between the profibrogenic responses in vitro and in vivo as
well as the ability of dispersed tubes to generate granulomatous inflammation and
fibrosis in airways. Tube dispersal also elicited more robust IL-1beta production
in THP-1 cells. While COOH-MWCNTs were poorly taken up in BEAS-2B and induced
little TGF-beta1 production, they were bioprocessed by AM and induced less
prominent collagen deposition at sites of nongranulomatous inflammation in the
alveolar region. Taken together, these results indicate that the dispersal state
of MWCNTs affects profibrogenic cellular responses that correlate with the extent
of pulmonary fibrosis and are of potential use to predict pulmonary toxicity.
PMID- 22047208
TI - Solid-phase synthesis of mimosine tetrapeptides and their inhibitory activities
on neuraminidase and tyrosinase.
AB - Neuraminidase is a rational target for influenza inhibition, and the search for
neuraminidase inhibitors has been intensified. Mimosine, a nonprotein amino acid,
was for the first time identified as a neuraminidase inhibitor with an IC(50) of
9.8 +/- 0.2 MUM. It was found that mimosine had slow, time-dependent competitive
inhibition against the neuraminidase. Furthermore, a small library of mimosine
tetrapeptides (M-A(1)-A(2)-A(3)) was synthesized by solid-phase synthesis and was
assayed to evaluate their neuraminidase and tyrosinase inhibitory properties.
Most of the tetrapeptides showed better activities than mimosine. Mimosine-FFY
was the best compound, and it exhibited 50% neuraminidase inhibition at a low
micromolar range of 1.8 +/- 0.2 MUM, whereas for tyrosinase inhibition, it had an
IC(50) of 18.3 +/- 0.5 MUM. The kinetic studies showed that all of the
synthesized peptides inhibited neuraminidase noncompetitively with K(i) values
ranging from 1.9 -to 7.2 MUM. These results suggest that mimosine could be used
as a source of bioactive compounds and may have possibilities in the design of
drugs as neuraminidase and tyrosinase inhibitors.
PMID- 22047210
TI - Phosphonic acid functionalized asymmetric phthalocyanines: synthesis,
modification of indium tin oxide, and charge transfer.
AB - Metalated and free-base A(3)B-type asymmetric phthalocyanines (Pcs) bearing, in
the asymmetric quadrant, a flexible alkyl linker of varying chain lengths
terminating in a phosphonic acid (PA) group have been synthesized. Two parallel
series of asymmetric Pc derivatives bearing aryloxy and arylthio substituents are
reported, and their synthesis and characterization through NMR, combustion
analysis, and MALDI-MS are described. We also demonstrate the modification of
indium tin oxide (ITO) substrates using the PA functionalized asymmetric Pc
derivatives and monitoring their electrochemistry. The PA functionalized
asymmetric Pcs were anchored to the ITO surface through chemisorption and their
electrochemical properties characterized using cyclic voltammetry to investigate
the effects of PA structure on the thermodynamics and kinetics of charge
transfer. Ionization energies of the modified ITO surfaces were measured using
ultraviolet photoemission spectroscopy.
PMID- 22047209
TI - The association between parity, infant gender, higher level of paternal education
and preterm birth in Pakistan: a cohort study.
AB - BACKGROUND: High rates of antenatal depression and preterm birth have been
reported in Pakistan. Self reported maternal stress and depression have been
associated with preterm birth; however findings are inconsistent. Cortisol is a
biological marker of stress and depression, and its measurement may assist in
understanding the influence of self reported maternal stress and depression on
preterm birth. METHODS: In a prospective cohort study pregnant women between 28
to 30 weeks of gestation from the Aga Khan Hospital for Women and Children
completed the A-Z Stress Scale and the Centre for Epidemiology Studies Depression
Scale to assess stress and depression respectively, and had a blood cortisol
level drawn. Women were followed up after delivery to determine birth outcomes.
Correlation coefficients and Wilcoxon rank sum test was used to assess
relationship between preterm birth, stress, depression and cortisol. Logistic
regression analysis was used to determine the key factors predictive of preterm
birth. RESULTS: 132 pregnant women participated of whom 125 pregnant women had
both questionnaire and cortisol level data and an additional seven had
questionnaire data only. Almost 20% of pregnant women (19.7%, 95% CI 13.3-27.5)
experienced a high level of stress and nearly twice as many (40.9%, 95% CI 32.4
49.8%) experienced depressive symptoms. The median of cortisol level was 27.40
ug/dl (IQR 22.5-34.2). The preterm birth rate was 11.4% (95% CI 6.5-18). There
was no relationship between cortisol values and stress scale or depression. There
was a significant positive relationship between maternal depression and stress.
Preterm birth was associated with higher parity, past delivery of a male infant,
and higher levels of paternal education. Insufficient numbers of preterm births
were available to warrant the development of a multivariable logistic regression
model. CONCLUSIONS: Preterm birth was associated with higher parity, past
delivery of a male infant, and higher levels of paternal education. There was no
relationship between stress, and depression, cortisol and preterm birth. There
were high rates of stress and depression among this sample suggesting that there
are missed opportunities to address mental health needs in the prenatal period.
Improved methods of measurement are required to better understand the
psychobiological basis of preterm birth.
PMID- 22047211
TI - Questionnaire of chronic illness care in primary care-psychometric properties and
test-retest reliability.
AB - BACKGROUND: The Chronic Care Model (CCM) is an evidence-based approach to
improving the structure of care for chronically ill patients with multimorbidity.
The Assessment of Chronic Illness Care (ACIC), an instrument commonly used in
international research, includes all aspects of the CCM, but cannot be easily
extended to the German context. A new instrument called the "Questionnaire of
Chronic Illness Care in Primary Care" (QCPC) was developed for use in Germany for
this reason. Here, we present the results of the psychometric properties and test
retest reliability of QCPC. METHODS: A total of 109 family doctors from different
German states participated in the validation study. Participating physicians
completed the QCPC, which includes items concerning the CCM and practice
structure, at baseline (T0) and 3 weeks later (T1). Internal consistency
reliability and test-retest reliability were evaluated using Cronbach's alpha and
Pearson's r, respectively. RESULTS: The QCPC contains five elements of the CCM
(decision support, delivery system design, self-management support, clinical
information systems, and community linkages). All subscales demonstrated moderate
internal consistency and moderate test-retest reliability over a three-week
interval. CONCLUSIONS: The QCPC is an appropriate instrument to assess the
structure of chronic illness care. Unlike the ACIC, the QCPC can be used by
health care providers without CCM training. The QCPC can detect the actual state
of care as well as areas for improvement of care according to the CCM.
PMID- 22047212
TI - Quantum chemistry study on internal conversion of diphenyldibenzofulvene in solid
phase.
AB - We investigate the nonradiative decay process of diphenyldibenzofulvene (DPDBF)
in solid phase by using the quantum chemistry methods. To carry out the
nonradiative rate constant calculation, we construct a solid phase model based on
the ONIOM method. The geometry of the DPDBF molecule is optimized for the ground
state by DFT and the first excited state by TD-DFT, and the corresponding
vibrational frequencies and normal coordinates are computed. Under displaced
distorted harmonic oscillator potential approximation, Huang-Rhys factors are
obtained. Vibronic coupling constants are calculated as a function of the normal
mode based on Domcke's scheme. We find that vibronic coupling constants of 12
modes with large reorganization energies are of similar order, and if this result
is still valid for other modes, the internal conversion rate would be determined
by high frequency modes because they have a significant nuclear factor that is
related to Franck-Condon overlap intergrals. We also find that geometrical
changes are suppressed due to the stacking effect, which yields small Huang-Rhys
values in the solid phase.
PMID- 22047217
TI - ERRATUM.
PMID- 22047218
TI - A transformative perspective on learning and professional development of Afghan
physiotherapists.
AB - The aim of this article is to explore factors that impacted learning of Afghan
physiotherapists in a development project to improve the physiotherapy services
in a disability programme implemented by a Swedish nongovernmental organisation
in Afghanistan. Participant observation, recorded as field notes, was used to
document the process, to gain a better understanding of professional development
of physiotherapists in Afghanistan. Field notes were analysed and factors
affecting learning were interpreted from a perspective inspired by transformative
learning. Various factors were identified: a pattern approach to treatment,
linear thinking, and socially oriented decision making affected how new things
learned were put into practice; concrete representations and an instrumental view
of knowledge characterised learning approaches; language barriers, different
interpretations of meaning, and cultural codes challenged communication; and a
prescriptive, encouraging approach of the expatriate physiotherapy development
worker affected teaching and learning. Working with professional development
across cultural borders is challenging, and the identified factors impacting
learning can help expatriate physiotherapists in adapting training to the Afghan
context. Exploring meaning perspectives and communicative learning could enhance
understanding of these factors for both expatriate and Afghan physiotherapists
and should be a focus in future development activities.
PMID- 22047220
TI - Correlation between Fischer-Tropsch catalytic activity and composition of
catalysts.
AB - This paper presents the synthesis and characterization of monometallic and
bimetallic cobalt and iron nanoparticles supported on alumina. The catalysts were
prepared by a wet impregnation method. Samples were characterized using
temperature-programmed reduction (TPR), temperature-programmed oxidation (TPO),
CO-chemisorption, transmission electron microscopy (TEM), field emission scanning
electron microscopy (FESEM-EDX) and N2-adsorption analysis. Fischer-Tropsch
synthesis (FTS) was carried out in a fixed-bed microreactor at 543 K and 1 atm,
with H2/CO = 2 v/v and space velocity, SV = 12L/g.h. The physicochemical
properties and the FTS activity of the bimetallic catalysts were analyzed and
compared with those of monometallic cobalt and iron catalysts at similar
operating conditions.H2-TPR analysis of cobalt catalyst indicated three
temperature regions at 506 degrees C (low), 650 degrees C (medium) and 731
degrees C (high). The incorporation of iron up to 30% into cobalt catalysts
increased the reduction, CO chemisorption and number of cobalt active sites of
the catalyst while an opposite trend was observed for the iron-riched bimetallic
catalysts. The CO conversion was 6.3% and 4.6%, over the monometallic cobalt and
iron catalysts, respectively. Bimetallic catalysts enhanced the CO conversion.
Amongst the catalysts studied, bimetallic catalyst with the composition of
70Co30Fe showed the highest CO conversion (8.1%) while exhibiting the same
product selectivity as that of monometallic Co catalyst. Monometallic iron
catalyst showed the lowest selectivity for C5+ hydrocarbons (1.6%).
PMID- 22047221
TI - Communication: A dynamical theory of homogeneous nucleation for colloids and
macromolecules.
AB - Homogeneous nucleation is formulated within the context of fluctuating
hydrodynamics. It is shown that for a colloidal system in the strong damping
limit the most likely path for nucleation can be determined by gradient descent
in density space governed by a nontrivial metric. This is illustrated by
application to low-density/high-density liquid transition of globular proteins in
solution where it is shown that nucleation process involves two stages: the
formation of an extended region with enhanced density followed by the formation
of a cluster within this region.
PMID- 22047222
TI - On the gauge invariance of nonperturbative electronic dynamics using the time
dependent Hartree-Fock and time-dependent Kohn-Sham.
AB - Nonperturbative electronic dynamics using the time-dependent Hartree-Fock (TDHF)
and time-dependent Kohn-Sham (TDKS) theories with the adiabatic approximation is
a powerful tool in obtaining insights into the interaction between a many
electron system and an external electromagnetic field. In practical applications
of TDHF/TDKS using a truncated basis set, the electronic dynamics and molecular
properties become gauge-dependent. Numerical simulations are carried out in the
length gauge and velocity gauge to verify the extent of gauge-dependence using
incomplete basis sets. Electronic dynamics of two many-electron systems, a helium
atom and a carbon monoxide molecule in high-intensity linearly polarized
radiation fields are performed using the TDHF and TDKS with two selected
adiabatic exchange-correlation (xc) functionals. The time evolution of the
expectation values of the dipole moment and harmonic spectra are calculated in
the two gauges, and the basis set dependence on the gauge-invariance of these
properties is investigated.
PMID- 22047223
TI - Relaxation mode analysis of a peptide system: comparison with principal component
analysis.
AB - This article reports the first attempt to apply the relaxation mode analysis
method to a simulation of a biomolecular system. In biomolecular systems, the
principal component analysis is a well-known method for analyzing the static
properties of fluctuations of structures obtained by a simulation and classifying
the structures into some groups. On the other hand, the relaxation mode analysis
has been used to analyze the dynamic properties of homopolymer systems. In this
article, a long Monte Carlo simulation of Met-enkephalin in gas phase has been
performed. The results are analyzed by the principal component analysis and
relaxation mode analysis methods. We compare the results of both methods and show
the effectiveness of the relaxation mode analysis.
PMID- 22047224
TI - Chemical reactions modulated by mechanical stress: extended Bell theory.
AB - A number of recent studies have shown that mechanical stress can significantly
lower or raise the activation barrier of a chemical reaction. Within a common
approximation due to Bell [Science 200, 618 (1978)], this barrier is linearly
dependent on the applied force. A simple extension of Bell's theory that includes
higher order corrections in the force predicts that the force-induced change in
the activation energy will be given by -FDeltaR - DeltachiF(2)/2. Here, DeltaR is
the change of the distance between the atoms, at which the force F is applied,
from the reactant to the transition state, and Deltachi is the corresponding
change in the mechanical compliance of the molecule. Application of this formula
to the electrocyclic ring-opening of cis and trans 1,2-dimethylbenzocyclobutene
shows that this extension of Bell's theory essentially recovers the force
dependence of the barrier, while the original Bell formula exhibits significant
errors. Because the extended Bell theory avoids explicit inclusion of the
mechanical stress or strain in electronic structure calculations, it allows a
computationally efficient characterization of the effect of mechanical forces on
chemical processes. That is, the mechanical susceptibility of any reaction
pathway is described in terms of two parameters, DeltaR and Deltachi, both
readily computable at zero force.
PMID- 22047225
TI - Short-time self-diffusion coefficient of a particle in a colloidal suspension
bounded by a microchannel: virial expansions and simulation.
AB - Self-diffusion of colloidal particles confined to a cylindrical microchannel is
considered theoretically and numerically. Virial expansion of the self-diffusion
coefficient is performed. Two-body and three-body hydrodynamic interactions are
evaluated with high precision using the multipole method. The multipole expansion
algorithm is also used to perform numerical simulations of the self-diffusion
coefficient, valid for all possible particle packing fractions. Comparison with
earlier results shows that the widely used method of reflections is insufficient
for calculations of hydrodynamic interactions even for small packing fractions
and small particles radii, contrary to the prevalent opinion.
PMID- 22047226
TI - Assessing weak hydrogen binding on Ca+ centers: an accurate many-body study with
large basis sets.
AB - Weak H(2) physisorption energies present a significant challenge to even the best
correlated theoretical many-body methods. We use the phaseless auxiliary-field
quantum Monte Carlo method to accurately predict the binding energy of Ca(+)
4H(2). Attention has recently focused on this model chemistry to test the
reliability of electronic structure methods for H(2) binding on dispersed
alkaline earth metal centers. A modified Cholesky decomposition is implemented to
realize the Hubbard-Stratonovich transformation efficiently with large Gaussian
basis sets. We employ the largest correlation-consistent Gaussian type basis sets
available, up to cc-pCV5Z for Ca, to accurately extrapolate to the complete basis
limit. The calculated potential energy curve exhibits binding with a double-well
structure.
PMID- 22047227
TI - Non-equilibrium spin-boson model: counting statistics and the heat exchange
fluctuation theorem.
AB - We focus on the non-equilibrium two-bath spin-boson model, a toy model for
examining quantum thermal transport in many-body open systems. Describing the
dynamics within the noninteracting-blip approximation equations, applicable,
e.g., in the strong system-bath coupling limit and/or at high temperatures, we
derive expressions for the cumulant generating function in both the Markovian and
non-Markovian limits by energy-resolving the quantum master equation of the
subsystem. For a Markovian bath, we readily demonstrate the validity of a steady
state heat exchange fluctuation theorem. In the non-Markovian limit a "weaker"
symmetry relation generally holds, a general outcome of microreversibility. We
discuss the reduction of this symmetry relation to the universal steady-state
fluctuation theorem. Using the cumulant generating function, an analytic
expression for the heat current is obtained. Our results establish the validity
of the steady-state heat exchange fluctuation theorem in quantum systems with
strong system-bath interactions. From the practical point of view, this study
provides tools for exploring transport characteristics of the two-bath spin-boson
model, a prototype for a nonlinear thermal conductor.
PMID- 22047228
TI - Optimized hierarchical equations of motion theory for Drude dissipation and
efficient implementation to nonlinear spectroscopies.
AB - Hierarchical equations of motion theory for Drude dissipation is optimized, with
a convenient convergence criterion proposed in advance of numerical propagations.
The theoretical construction is on the basis of a Pade spectrum decomposition
that has been qualified to be the best sum-over-poles scheme for quantum
distribution function. The resulting hierarchical dynamics under the a priori
convergence criterion are exemplified with a benchmark spin-boson system, and
also the transient absorption and related coherent two-dimensional spectroscopy
of a model exciton dimer system. We combine the present theory with several
advanced techniques such as the block hierarchical dynamics in mixed Heisenberg
Schrodinger picture and the on-the-fly filtering algorithm for the efficient
evaluation of third-order optical response functions.
PMID- 22047229
TI - Ab initio properties of Li-group-II molecules for ultracold matter studies.
AB - We perform a systematic investigation of the electronic properties of the
(2)Sigma(+) ground state of Li-alkaline-earth dimers. These molecules are
proposed as possible candidates for quantum simulation of lattice-spin models. We
apply powerful quantum chemistry coupled-cluster method and large basis sets to
calculate potential energies and permanent dipole moments for the LiBe, LiMg,
LiCa, LiSr, and LiYb molecules. Agreement of calculated molecular constants with
existing experimental data is better than or equal to 8%. Our results reveal a
surprising irregularity in the dissociation energy and bond length with an
increase in the reduced mass of the molecule. At the same time, the permanent
dipole moment at the equilibrium separation has the smallest value between 0.01
a.u. and 0.1 a.u. for the heaviest (LiSr and LiYb) molecules and increases to 1.4
a.u. for the lightest (LiBe), where 1 a.u. is one atomic unit of dipole moment.
We consider our study of the (2)Sigma(+) molecules a first step towards a
comprehensive analysis of their interactions in an optical trap.
PMID- 22047230
TI - Geometry optimization of bimetallic clusters using an efficient heuristic method.
AB - In this paper, an efficient heuristic algorithm for geometry optimization of
bimetallic clusters is proposed. The algorithm is mainly composed of three
ingredients: the monotonic basin-hopping method with guided perturbation (MBH
GP), surface optimization method, and iterated local search (ILS) method, where
MBH-GP and surface optimization method are used to optimize the geometric
structure of a cluster, and the ILS method is used to search the optimal homotop
for a fixed geometric structure. The proposed method is applied to Cu(38-n)Au(n)
(0 <= n <= 38), Ag(55-n)Au(n) (0 <= n <= 55), and Cu(55-n)Au(n) (0 <= n <= 55)
clusters modeled by the many-body Gupta potential. Comparison with the results
reported in the literature indicates that the present method is highly efficient
and a number of new putative global minima missed in the previous papers are
found. The present method should be a promising tool for the theoretical
determination of ground-state structure of bimetallic clusters. Additionally,
some key elements and properties of the present method are also analyzed.
PMID- 22047231
TI - Dispersion, static correlation, and delocalisation errors in density functional
theory: an electrostatic theorem perspective.
AB - Dispersion, static correlation, and delocalisation errors in density functional
theory are considered from the unconventional perspective of the force on a
nucleus in a stretched diatomic molecule. The electrostatic theorem of Feynman is
used to relate errors in the forces to errors in the electron density
distortions, which in turn are related to erroneous terms in the Kohn-Sham
equations. For H(2), the exact dispersion force arises from a subtle density
distortion; the static correlation error leads to an overestimated force due to
an exaggerated distortion. For H(2)(+), the exact force arises from a delicate
balance between attractive and repulsive components; the delocalisation error
leads to an underestimated force due to an underestimated distortion. The net
force in H(2)(+) can become repulsive, giving the characteristic barrier in the
potential energy curve. Increasing the fraction of long-range exact orbital
exchange increases the distortion, reducing delocalisation error but increasing
static correlation error.
PMID- 22047232
TI - Extended Lagrangian free energy molecular dynamics.
AB - Extended free energy Lagrangians are proposed for first principles molecular
dynamics simulations at finite electronic temperatures for plane-wave
pseudopotential and local orbital density matrix-based calculations. Thanks to
the extended Lagrangian description, the electronic degrees of freedom can be
integrated by stable geometric schemes that conserve the free energy. For the
local orbital representations both the nuclear and electronic forces have simple
and numerically efficient expressions that are well suited for reduced complexity
calculations. A rapidly converging recursive Fermi operator expansion method that
does not require the calculation of eigenvalues and eigenfunctions for the
construction of the fractionally occupied density matrix is discussed. An
efficient expression for the Pulay force that is valid also for density matrices
with fractional occupation occurring at finite electronic temperatures is also
demonstrated.
PMID- 22047233
TI - Solvation effects on angular distributions in H- (NH3)n and NH2(-) (NH3)n
photodetachment: role of solute electronic structure.
AB - We report 355 and 532 nm photoelectron imaging results for H(-)(NH(3))(n) and
NH(2)(-)(NH(3))(n), n = 0-5. The photoelectron spectra are consistent with the
electrostatic picture of a charged solute (H(-) or NH(2)(-)) solvated by n
ammonia molecules. For a given number of solvent molecules, the NH(2)(-) core
anion is stabilized more strongly than H(-), yet the photoelectron angular
distributions for solvated H(-) deviate more strongly from the unsolvated limit
than those for solvated NH(2)(-). Hence, we conclude that solvation effects on
photoelectron angular distributions are dependent on the electronic structure of
the anion, i.e., the type of the initial orbital of the photodetached electron,
rather than merely the strength of solvation interactions. We also find evidence
of photofragmentation and autodetachment of NH(2)(-)(NH(3))(2-5), as well as
autodetachment of H(-)(NH(3))(5), upon 532 nm excitation of these species.
PMID- 22047234
TI - Photoelectron angular distributions in negative-ion photodetachment from mixed sp
states.
AB - We describe an approach for constructing analytical models for the energy
dependence of photoelectron angular distributions in the one-electron, non
relativistic approximation. We construct such a model for electron emission from
an orbital described as a superposition of s- and p-type functions, using
linearly polarized light. In the limits of pure s or pure p electron
photodetachment or photoionization, the model correctly reproduces the familiar
Cooper-Zare formula. The model predictions are compared to experimental results
for strongly solvated H(-) and NH(2)(-), corresponding to predominantly s and
predominantly p character parent states, respectively.
PMID- 22047235
TI - A theoretical study of hydrogen- and lithium-bonded complexes of F-H/Li and Cl
H/Li with NF3, NH3, and NH2(CH3).
AB - Hydrogen- and lithium-bonded complexes of A-H/Li (A = F, Cl) with the amine
analogues NF(3), NH(3), and NH(2)(CH(3)) were studied at the MP2/6-311++G(d,p)
level of theory. Bond extensions and redshifts were obtained for the H-bonded
complexes, while bond extensions and blueshifts were obtained for the Li-bonded
species. The variation of these and other properties with the basicity of the
amines was investigated and rationalized by comparing the ab initio results with
predictions from a model derived from perturbation theory.
PMID- 22047236
TI - Control of vibronic excitation using quantum-correlated photons.
AB - We theoretically investigate the two-step excitation of a molecular vibronic
state using quantum-correlated photons with time delay in order to control the
population of the vibronic excited state. A Morse oscillator having three sets of
vibronic states, namely, the ground state, intermediate states, and excited
states, is used to evaluate the efficiency of the two-step excitation process. We
show that we can efficiently and selectively excite only a target state by using
correlated photons and can control the excitation population of the target state
by adjusting the delay time of the correlated photons. The potential of
controlling a chemical reaction using correlated photons is also discussed.
PMID- 22047237
TI - Ab initio quantum dynamical study of photoinduced ring opening in furan.
AB - The nonadiabatic photoinduced ring opening occurring in the two lowest excited
singlet states of furan is investigated theoretically, using wave-packet
propagation techniques. The underlying multidimensional potential energy surfaces
(PESs) are obtained from ab initio computations, using the equation-of-motion
coupled cluster method restricted to single and double excitations (EOM-CCSD),
reported in earlier recent work [E. V. Gromov, A. B. Trofimov, F. Gatti, and H.
Koppel, J. Chem. Phys. 133, 164309 (2010)]. Up to five nuclear degrees of freedom
are considered in the quantum dynamical treatment. Four of them represent in
plane motion for which the electronic states in question (correlating with the
valence (1)B(2)(V) and Rydberg (1)A(2)(3s) states at the C(2v) ground-state
molecular configuration) have different symmetries, A(') and A(''), respectively.
The fifth mode, representing out-of-plane bending of the oxygen atom against the
carbon-atom plane, leads to an interaction of these states, as is crucial for the
photoreaction. The nonadiabatic coupling and conical intersection cause an
electronic population transfer on the order of ~10 fs. Its main features, and
that of the wave-packet motion, are interpreted in terms of properties of the
PES. The lifetime due to the ring-opening process has been estimated to be around
2 ps. The dependence of this estimate on the nuclear degrees of freedom retained
in the computations is discussed.
PMID- 22047238
TI - Theoretical investigation of the photophysics of methyl salicylate isomers.
AB - The photophysics of methyl salicylate (MS) isomers has been studied using time
dependent density functional theory and large basis sets. First electronic
singlet and triplet excited states energies, structure, and vibrational analysis
were calculated for the ketoB, enol, and ketoA isomers. It is demonstrated that
the photochemical pathway involving excited state intramolecular proton transfer
(ESIPT) from the ketoB to the enol tautomer agrees well with the dual
fluorescence in near-UV (from ketoB) and blue (from enol) wavelengths obtained
from experiments. Our calculation confirms the existence of a double minimum in
the excited state pathway along the O-H-O coordinate corresponding to two
preferred energy regions: (1) the hydrogen belongs to the OH moiety and the
structure of methyl salicylate is ketoB; (2) the hydrogen flips to the closest
carboxyl entailing electronic rearrangement and tautomerization to the enol
structure. This double well in the excited state is highly asymmetric. The Franck
Condon vibrational overlap is calculated and accounts for the broadening of the
two bands. It is suggested that forward and backward ESIPT through the barrier
separating the two minima is temperature-dependent and affects the intensity of
the fluorescence as seen in experiments. When the enol fluoresces and returns to
its ground state, a barrier-less back proton transfer repopulates the ground
state of methyl salicylate ketoB. It is also demonstrated that the rotamer ketoA
is not stable in an excited state close to the desired emission wavelength. This
observation eliminates the conjecture that the near-UV emission of the dual
fluorescence originates from the ketoA rotamer. New experimental results for pure
MS in the liquid state are reported and theoretical results compared to them.
PMID- 22047239
TI - Interpretation of the photoelectron spectra of superalkali species: Li3O and Li3O
.
AB - The present paper deals with the interpretation of the photoelectron spectrum of
the Li(3)O(-). After several failed attempts to attribute all of the observed
peaks in the experimental spectrum to anionic species, neutral species were
considered assuming a sequential two-photon absorption mechanism. We find that
only two of the six observed peaks can be attributed to photodetachments and that
all other observed features can be assigned to ionizations from the ground and
excited states of the neutral. Nuclear distributions other than three lithium
atoms surrounding the oxygen are not likely to be stable. The interpretation of
the experimental peak located at about 1.2 eV remains challenging. It can either
be attributed to the second electron detachment (involving the HOMO -1 orbital)
energy from the anion's triplet C(2v) state or to higher excited states
(involving HOMO +10, 11, 12... orbitals) of the neutral species. Furthermore, we
have examined the influence of vibrational displacements on the location of the
observed peaks. We find that this effect is smaller than 0.05 eV and, therefore,
must be considered as negligible.
PMID- 22047240
TI - Photoelectron spectroscopy of the molecular anions, Li3O- and Na3O-.
AB - The molecular anions, Li(3)O(-) and Na(3)O(-) were produced by laser vaporization
and studied via anion photoelectron spectroscopy. Li(3)O(-) and Na(3)O(-) are the
negative ions of the super-alkali neutral molecules, Li(3)O and Na(3)O. A two
photon process involving the photodetachment of electrons from the Li(3)O(-) and
Na(3)O(-) anions and the photoionization of electrons from the resulting Li(3)O
and Na(3)O neutral states was observed. The assignment of the Li(3)O(-)
photoelectron spectrum was based on computational results provided by Zein and
Ortiz [J. Chem. Phys. 135, 164307 (2011)].
PMID- 22047241
TI - Ultrafast non-adiabatic dynamics of methyl substituted ethylenes: the pi3s
Rydberg state.
AB - Excited state unimolecular reactions of some polyenes exhibit localization of
their dynamics at a single ethylenic double bond. Here we present studies of the
fundamental photophysical processes in the ethylene unit itself. Combined
femtosecond time-resolved photoelectron spectroscopy (TRPES) and ab initio
quantum chemical calculations was applied to the study of excited state dynamics
in cis-butene, trans-butene, trimethylethylene, and tetramethylethylene,
following initial excitation to their respective pi3s Rydberg states. The
wavelength dependence of the pi3s Rydberg state dynamics of tetramethylethylene
was investigated in more detail. The pi3s Rydberg to pipi(*) valence state decay
rate varies greatly with substituent: the 1,2-di- and tri-methyl substituted
ethylenes (cis-butene, trans-butene, and trimethylethylene) show an ultrafast
decay (~20 fs), whereas the fully methylated tetramethylethylene shows a decay
rate of 2 to 4 orders of magnitude slower. These observations are rationalized in
terms of topographical trends in the relevant potential energy surfaces, as found
from ab initio calculations: (1) the barrier between the pi3s state and the pipi*
state increases with increasing methylation, and (2) the pi3s/pipi* minimum
energy conical intersection displaces monotonically away from the pi3s Franck
Condon region with increasing methylation. The use of systematic methylation in
combination with TRPES and ab initio computation is emerging as an important tool
in discerning the excited state dynamics of unsaturated hydrocarbons.
PMID- 22047242
TI - Vibronic coupling in the A2Pi and B2Sigma+ electronic states of the NCS radical.
AB - The spin-rovibronic energy levels of the A(2)Pi and B(2)Sigma(+) electronic
states of thiocyanate radical have been calculated variationally, using high
level ab initio coupled diabatic potential energy surfaces. Computations up to J
= 7/2 have been performed, obtaining all levels with K <= 3
(Sigma(1/2),Pi(1/2,3/2),Delta(3/2,5/2),Phi(5/2,7/2)), for energies up to 2000 cm(
1) above the A(000)(2)Pi(3/2) level. The available experimental data have been
critically reviewed in the light of the theoretical findings.
PMID- 22047243
TI - New ab initio coupled potential energy surfaces for the Br(2P(3/2), 2P(1/2)) + H2
reaction.
AB - The three lowest (1A('), 2A('), and 1A('')) adiabatic potential energy surfaces
(PESs) for the Br((2)P) + H(2) reactive system have been computed based on the
multi-reference configuration interaction (MRCI) method including the Davidson's
correction with a large basis set. These three adiabatic PESs have been
transformed to a diabatic representation, leading to four coupling potentials. In
addition, the spin-orbit matrix elements were also obtained using the Breit-Pauli
Hamiltonian and the unperturbed MRCI wavefunctions in the Br + H(2) channel and
the transition state region. Consequently, six coupling potentials were obtained
and their characteristics were extensively discussed. Nonadiabatic quantum
dynamics calculations for this system have been realized with these realistic
diabatic potentials instead of previous semi-empirical diabatic potentials. Based
on two-state model nonadiabatic calculations for the Br((2)P(3/2), (2)P(1/2)) +
H(2) reaction, the Br((2)P(1/2)) + H(2) reaction was found to show less
reactivity than the Br((2)P(3/2)) + H(2) reaction at collision energies beyond
the threshold of the Br((2)P(3/2)) + H(2) reaction. Our results are consistent
with the previous studies on the XH(2) (X = F, Cl) system, which indicate that
the adiabatically forbidden channel is dominant at low energies in the open-shell
halogen atom plus H(2) reactions.
PMID- 22047244
TI - State-to-state quantum dynamics of the N(4S) + OH(X2Pi) -> H(2S) + NO(X 2Pi)
reaction.
AB - Quantum state-to-state dynamics for the N((4)S) + OH(X( 2)Pi) -> H((2)S) + NO(X(
2)Pi) reaction is reported on an accurate ab initio potential energy surface of
the lowest triplet electronic state (a(3)A(")) of HNO/HON. It was found that the
reaction is dominated by long-lived resonances supported by the HNO and HON
wells. Significant non-reactive scattering was observed, indicating substantial
deviations from the statistical limit. Due to the large exothermicity of the
reaction, the NO product has hot internal state distributions: its rotational
state distribution is inverted and peaks near the highest accessible rotational
level; and its vibrational state distribution extends to upsilon = 10 and decays
monotonically with the vibrational quantum number. In particular, the predicted
product vibrational distribution is in reasonably good agreement with experiment.
The calculated differential cross section is dominated by scattering in both the
forward and backward directions, consistent with the formation of reaction
intermediates.
PMID- 22047246
TI - Structure and dynamics of 1,2-dimethoxyethane and 1,2-dimethoxypropane in aqueous
and non-aqueous solutions: a molecular dynamics study.
AB - Herein, we report a comparative modelling study of 1,2-dimethoxyethane (DME) and
1,2-dimethoxypropane (DMP) at 298 K and 318 K in the liquid state, water
mixtures, and at infinite dilution condition in water, methanol, carbon
tetrachloride, and n-heptane. Both DME and DMP are united-atom models compatible
with GROMOS/OPLS force fields. Calculated thermodynamic and structural properties
of the pure DME and DMP liquids resulted in excellent agreement with the
experimental data. In aqueous solutions, densities, diffusion coefficients, and
concentration dependent conformers of DME, were in agreement with experimental
data. The calculated free energy of solvation (DeltaG(hyd)) at 298 K is equal to
22.1 +/- 0.8 kJ mol(-1) in good agreement with the experimental value of 20.2 kJ
mol(-1). In addition, the free energy of solvation of DME in non-aqueous solvents
follows the trend methanol ~ water < carbon tetrachloride < n-heptane,
consistently with the dielectric constant of the solvents. On contrary, the
presence of an extra methyl group on chiral carbon makes DMP less soluble than
DME in water (DeltaG(hyd) = -16.0 +/- 1.1 kJ mol(-1)) but more soluble in non
polar solvents as n-heptane. Finally, for the DMP the chiral discrimination of
the two enantiomers was calculated as solvation free energy difference of one DMP
isomer in the solution of the other. The obtained value of DeltaDeltaG(RS) = -3.7
+/- 1.4 kJ mol(-1) indicates a net chiral discrimination of the two enantiomers.
PMID- 22047247
TI - Inverse Raman bands in ultrafast Raman loss spectroscopy.
AB - Ultrafast Raman loss spectroscopy (URLS) is equivalent to anti-Stokes femtosecond
stimulated Raman spectroscopy (FSRS), using a broadband probe pulse that extends
to the blue of the narrow bandwidth Raman pump, and can be described as inverse
Raman scattering (IRS). Using the Feynman dual time-line diagram, the third-order
polarization for IRS with finite pulses can be written down in terms of a four
time correlation function. An analytic expression is obtained for the latter in
the harmonic approximation which facilitates computation. We simulated the URLS
of crystal violet (CV) for various resonance Raman pump excitation wavelengths
using the IRS polarization expression with finite pulses. The calculated results
agreed well with the experimental results of S. Umapathy et al., J. Chem. Phys.
133, 024505 (2010). In the limit of monochromatic Raman pump and probe pulses, we
obtain the third-order susceptibility for multi-modes, and for a single mode we
recover the well-known expression for the third-order susceptibility, chi(IRS)
((3)), for IRS. The latter is used to understand the mode dependent phase changes
as a function of Raman pump excitation in the URLS of CV.
PMID- 22047248
TI - Static and pulsed field gradient nuclear magnetic resonance studies of water
diffusion in protein matrices.
AB - Static field gradient and pulsed field gradient NMR are used to study the
temperature dependence of water diffusion in myoglobin and lysozyme matrices for
low hydration levels of about 0.3 g/g. We show that in order to determine
reliable self-diffusion coefficients D in a broad temperature range, it is very
important to consider an exchange of magnetization between water and protein
protons, often denoted as cross relaxation. Specifically, upon cooling, the
observed stimulated-echo decays, which reflect water diffusion near ambient
temperature, become more and more governed by cross relaxation. We demonstrate
that comparison of experimental results for inhomogeneous and homogeneous
magnetic fields enables successful separation of diffusion and relaxation
contributions to the stimulated-echo decays. Making use of this possibility, we
find that in the temperature range 230-300 K, the temperature-dependent
diffusivities D exhibit a Vogel-Fulcher-Tammann behavior, where water diffusion
in the studied protein matrices is substantially slower than in the bulk. By
comparing present and previous data, we discuss relations between translational
and rotational motions and between short-range and long-range water dynamics in
protein matrices. In addition, we critically examine the significance of results
from previous applications of NMR diffusometry to the temperature-dependent water
diffusion in protein matrices.
PMID- 22047249
TI - Response of solid Ne upon photoexcitation of a NO impurity: a quantum dynamics
study.
AB - The ultrafast geometrical rearrangement dynamics of NO doped cryogenic Ne
matrices after femtosecond laser pulse excitation is studied using a quantum
dynamical approach based on a multi-dimensional shell model, with the shell radii
being the dynamical variables. The Ne-NO interaction being only weakly
anisotropic allows the model to account for the main dynamical features of the
rare gas solid. Employing quantum wave packet propagation within the time
dependent Hartree approximation, both, the static deformation of the solid due to
the impurity and the dynamical response after femtosecond excitation, are
analysed. The photoinduced dynamics of the surrounding rare gas atoms is found to
be a complex high-dimensional process. The approach allows to consider realistic
time-dependent femtosecond pulses and the effect of the pulse duration is clearly
shown. Finally, using the pulse parameters of previous experiments, pump-probe
signals are calculated and found to be in good agreement with experimental
results, allowing for a clear analysis of the ultrafast mechanism of the energy
transfer into the solid.
PMID- 22047250
TI - Vibrational energy transfer and anisotropy decay in liquid water: is the Forster
model valid?
AB - Ultrafast pump-probe anisotropy experiments have been performed on liquid H(2)O
and D(2)O. In both cases, the anisotropy decay is extremely fast (on the order of
100 or 200 fs) and is presumed due to resonant vibrational energy transfer. The
experiments have been interpreted in terms of the Forster theory, wherein the
rate constant for intermolecular hopping transport is proportional to the inverse
sixth power of the distance between the vibrational chromophores. In particular,
the anisotropy decay is assumed to be simply related to the survival probability
as calculated with the Forster theory. While the theory fits the data well, and
is a reasonable model for these systems, there are several assumptions in the
theory that might be suspect for water. Using our mixed quantum/classical model
for vibrational spectroscopy and dynamics in liquid water, which agrees well with
anisotropy decay experiments on the pure liquids as well as H(2)O/D(2)O mixtures,
we critically analyze both the survival probability and anisotropy decay, in
order to assess the applicability of the Forster theory.
PMID- 22047252
TI - Pair force distributions in simple fluids.
AB - Analytic expressions are derived for the frequency distribution, P(f), of pair
forces, f, and those of their alpha-Cartesian component, f(alpha), or
P(f(alpha)), for some typical model simple fluids, expressed in terms of the
radial distribution function and known constants. For strongly repulsive inverse
power (IP), exponential and Yukawa purely repulsive potentials, P(f) diverges at
the origin approximately as ~f(-1), but with different limiting analytic forms.
P(f(alpha)) is also shown to diverge as ~f(-1) as f -> 0 for the IP fluid. For
the Lennard-Jones potential fluid, P(f) is finite for all f >= 0 but has two
singularities for negative f, corresponding to the zero force limit (i.e., f ->
0(-)) and the point of inflection in the potential. The corresponding component
force distribution is singular as f(alpha) -> 0 from both positive and negative
force sides. The large force limit of P(f), which originates from the close
neighbor interactions, is nearly exponential for the IP and LJ fluids, as is also
found for granular materials. A more complete picture of force distributions in
off-lattice particulate systems as a function of force law and state point
(particularly the extent of "thermalization" of the particles) is provided.
PMID- 22047251
TI - Vibrational spectroscopy of water in hydrated lipid multi-bilayers. II. Two
dimensional infrared and peak shift observables within different theoretical
approximations.
AB - In a previous report, we calculated the infrared absorption spectrum and both the
isotropic and anisotropic pump-probe signals for the OD stretch of isotopically
dilute water in dilauroylphosphatidylcholine (DLPC) multi-bilayers as a function
of the lipid hydration level. These results were then compared to recent
experimental measurements and are in generally good agreement. In this paper, we
will further investigate the structure and dynamics of hydration water using
molecular dynamics simulations and calculations of the two-dimensional infrared
and vibrational echo peak shift observables for hydration water in DLPC
membranes. These observables have not yet been measured experimentally, but
future comparisons may provide insight into spectral diffusion processes and
hydration water heterogeneity. We find that at low hydration levels the motion of
water molecules inside the lipid membrane is significantly arrested, resulting in
very slow spectral diffusion. At higher hydration levels, spectral diffusion is
more rapid, but still slower than in bulk water. We also investigate the effects
of several common approximations on the calculation of spectroscopic observables
by computing these observables within multiple levels of theory. The impact of
these approximations on the resulting spectra affects our interpretation of these
measurements and reveals that, for example, the cumulant approximation, which may
be valid for certain systems, is not a good approximation for a highly
heterogeneous environment such as hydration water in lipid multi-bilayers.
PMID- 22047253
TI - Simulated pressure response of crystalline indole.
AB - The isostatic pressure response of crystalline indole up to 25 GPa was
investigated through static geometry optimization using Tkatchenko-Scheffler
dispersion-corrected density functional theory method. Different symmetries were
identified in the structural evolution with increased pressure, but no motif
transition was observed, owing to the stability of the herringbone (HB) motif for
small polycyclic aromatic hydrocarbons. Hirshfeld surface analysis determined
that there was an increase in the fraction of H...pi and pi...pi contacts within
the high pressure structures, while the fraction of H...H contacts was lowered
via geometric rearrangements. It was found that isostatic pressure alone, up to
25 GPa, was not sufficient to induce a chemical reaction due to the poor pi
orbital overlap existing within the HB motif. However, the applied pressure sets
the stage for an activated chemical reaction when the molecules approach each
other along the long molecular axis, with a reaction energy and reaction barrier
of 1.05 eV and 1.80 eV per molecular unit, respectively.
PMID- 22047255
TI - Computer simulation study of thermodynamic scaling of dynamics of
2Ca(NO3)2.3KNO3.
AB - Molecular dynamics (MD) simulations of the glass-former 2Ca(NO(3))(2.3KNO(3),
CKN, were performed as a function of temperature at pressures 0.1 MPa, 0.5 GPa,
1.0 GPa, and 2.0 GPa. Diffusion coefficient, relaxation time of the intermediate
scattering function, and anion reorientational time were obtained as a function
of temperature and densitiy rho. These dynamical properties of CKN scale as
rho(gamma)/T with a common value gamma = 1.8 +/- 0.1. The scaling parameter gamma
is consistent with the exponent of the repulsive part of an effective
intermolecular potential for the repulsion between the atoms at shortest distance
in the equilibrium structure of liquid CKN, Ca(2+), and oxygen atoms of NO(3)(-).
Correlation between potential energy and virial is obeyed for the short-range
terms of the potential function, but not for the whole potential including
coulombic interactions. Decoupling of diffusion coefficient and reorientational
relaxation time from relaxation time take place at a given rho(gamma)/T value,
i.e., breakdown of Stokes-Einstein and Debye-Stokes-Einstein equations result
from combined thermal and volume effects. The MD results agree with correlations
proposed between long-time relaxation and short-time dynamics, lntau ? 1/,
where the mean square displacement concerns a time window of 10.0 ps. It
has been found that scales as rho(gamma)/T above and below the glass
transition temperature, so that thermodynamic scaling of liquid dynamics can be
thought as a consequence of theories relating short- and long-time dynamics, and
the more fundamental scaling concerns short-time dynamical properties.
PMID- 22047254
TI - X-ray Raman scattering provides evidence for interfacial acetonitrile-water
dipole interactions in aqueous solutions.
AB - Aqueous solutions of acetonitrile (MeCN) have been studied with oxygen K-edge x
ray Raman scattering (XRS) which is found to be sensitive to the interaction
between water and MeCN. The changes in the XRS spectra can be attributed to water
directly interacting with MeCN and are reproduced by density functional theory
calculations on small clusters of water and MeCN. The dominant structural
arrangement features dipole interaction instead of H-bonds between the two
species as revealed by the XRS spectra combined with spectrum calculations. Small
angle x-ray scattering shows the largest heterogeneity for a MeCN to water ratio
of 0.4 in agreement with earlier small-angle neutron scattering data.
PMID- 22047256
TI - Dynamic mechanism of equivalent conductivity minimum of electrolyte solution.
AB - The theory on electric conductivity of electrolyte solutions we have developed
[T. Yamaguchi, T. Matsuoka, and S. Koda, J. Chem. Phys. 127, 064508 (2007)] is
applied to a model electrolyte solution that shows a minimum of equivalent
conductivity as the function of concentration [T. Yamaguchi, T. Akatsuka, and S.
Koda, J. Chem. Phys. 134, 244506 (2011)]. The theory succeeds in reproducing the
equivalent conductivity minimum, whereas the mode-coupling theory (MCT)
underestimates the conductivity in the low-concentration regime. The theory can
also reproduce the decrease in the relaxation time of conductivity with
increasing the concentration we have demonstrated with a Brownian dynamics
simulation. A detailed analysis shows that the relaxation of the conductivity
occurs through two processes. The faster one corresponds to the collision between
a cation and an anion, and the slower one does to the polarization of the ionic
atmosphere. The increase in the equivalent conductivity with concentration is
attributed to the decrease in the effect of the ionic atmosphere, which is in
turn explained by the fact that the counter ion cannot penetrate into the
repulsive core when the Debye screening length is compatible or smaller than the
ionic diameter. The same mechanism is also observed in MCT calculation with
static structure factor determined by mean-spherical approximation.
PMID- 22047257
TI - A few simple rules governing hydrogenation of graphene dots.
AB - We investigated binding of hydrogen atoms to small polycyclic aromatic
hydrocarbons (PAHs)--i.e., graphene dots with hydrogen-terminated edges--using
density functional theory and correlated wavefunction techniques. We considered a
number of PAHs with three to seven hexagonal rings and computed binding energies
for most of the symmetry unique sites, along with the minimum energy paths for
significant cases. The chosen PAHs are small enough to not present radical
character at their edges, yet show a clear preference for adsorption at the edge
sites which can be attributed to electronic effects. We show how the results, as
obtained at different levels of theory, can be rationalized in detail with the
help of a few simple concepts derivable from a tight-binding model of the pi
electrons.
PMID- 22047258
TI - Charge transfer interactions of a Ru(II) dye complex and related ligand molecules
adsorbed on Au(111).
AB - The interaction of the dye molecule, N3 (cis-bis(isothiocyanato)bis(2,2(')
bipyridyl-4,4(')-dicarboxylato)-ruthenium(II)), and related ligand molecules with
a Au(111) surface has been studied using synchrotron radiation-based electron
spectroscopy. Resonant photoemission spectroscopy (RPES) and autoionization of
the adsorbed molecules have been used to probe the coupling between the molecules
and the substrate. Evidence of charge transfer from the states near the Fermi
level of the gold substrate into the lowest unoccupied molecular orbital (LUMO)
of the molecules is found in the monolayer RPES spectra of both isonicotinic acid
and bi-isonicotinic acid (a ligand of N3), but not for the N3 molecule itself.
Calibrated x-ray absorption spectroscopy and valence band spectra of the
monolayers reveals that the LUMO crosses the Fermi level of the surface in all
cases, showing that charge transfer is energetically possible both from and to
the molecule. A core-hole clock analysis of the resonant photoemission reveals a
charge transfer time of around 4 fs from the LUMO of the N3 dye molecule to the
surface. The lack of charge transfer in the opposite direction is understood in
terms of the lack of spatial overlap between the pi*-orbitals in the aromatic
rings of the bi-isonicotinic acid ligands of N3 and the gold surface.
PMID- 22047259
TI - Adsorption, diffusion, dewetting, and entrapment of acetone on Ni(111), surface
modified silicon, and amorphous solid water studied by time-of-flight secondary
ion mass spectrometry and temperature programmed desorption.
AB - Interactions of acetone with the silicon surfaces terminated with hydrogen,
hydroxyl, and perfluorocarbon are investigated; results are compared to those on
amorphous solid water (ASW) to gain insights into the roles of hydrogen bonds in
surface diffusion and hydration of acetone adspecies. The surface mobility of
acetone occurs at ~60 K irrespective of the surface functional groups.
Cooperative diffusion of adspecies results in a 2D liquid phase on the H- and
perfluorocarbon-terminated surfaces, whereas cooperativity tends to be quenched
via hydrogen bonding on the OH-terminated surface, thereby forming residues that
diffuse slowly on the surface after evaporation of the physisorbed species (i.e.,
2D liquid). The interaction of acetone adspecies on the non-porous ASW surface
resembles that on the OH-terminated Si surface, but the acetone molecules tend to
be hydrated on the porous ASW film, as evidenced by their desorption during the
glass-liquid transition and crystallization of water. The roles of micropores in
hydration of acetone molecules are discussed from comparison with the results
using mesoporous Si substrates.
PMID- 22047260
TI - Continuous-time photon-stimulated desorption spectroscopy studies on soft x-ray
induced reactions of CF3Br adsorbed on Si(111)-7*7.
AB - Continuous-time core-level photon-stimulated desorption (PSD) spectroscopy was
used to study the soft x-ray-induced reactions of CF(3)Br molecules adsorbed on
Si(111)-7*7 near the Si(2p) edge (98-110 eV). The monochromatic synchrotron
radiation was employed as a soft x-ray light source in the photon-induced
reactions and also as a probe for investigating the produced fluorination states
of the bonding surface Si atom in the positive-ion PSD spectroscopy. Several
different surface coverages were investigated. The PSD spectra from the low
CF(3)Br-covered surfaces show the production of surface SiF species, while those
from the high-CF(3)Br-covered surfaces depict the formation of surface SiF,
SiF(2), and SiF(3) species. The photolysis cross section of the submonolayer
CF(3)Br-covered surface is determined as ~4.3*10(-18) cm(2). A comparison with
the results on CF(3)Cl/Si(111)-7*7 surface is discussed.
PMID- 22047261
TI - Potential of mean force between identical charged nanoparticles immersed in a
size-asymmetric monovalent electrolyte.
AB - In a previous theoretical and simulation study [G. I. Guerrero-Garcia, E.
Gonzalez-Tovar, and M. Olvera de la Cruz, Soft Matter 6, 2056 (2010)], it has
been shown that an asymmetric charge neutralization and electrostatic screening
depending on the charge polarity of a single nanoparticle occurs in the presence
of a size-asymmetric monovalent electrolyte. This effect should also impact the
effective potential between two macroions suspended in such a solution. Thus, in
this work we study the mean force and the potential of mean force between two
identical charged nanoparticles immersed in a size-asymmetric monovalent
electrolyte, showing that these results go beyond the standard description
provided by the well-known Derjaguin-Landau-Verwey-Overbeek theory. To include
consistently the ion-size effects, molecular dynamics (MD) simulations and liquid
theory calculations are performed at the McMillan-Mayer level of description in
which the solvent is taken into account implicitly as a background continuum with
the suitable dielectric constant. Long-range electrostatic interactions are
handled properly in the simulations via the well established Ewald sums method
and the pre-averaged Ewald sums approach, originally proposed for homogeneous
ionic fluids. An asymmetric behavior with respect to the colloidal charge
polarity is found for the effective interactions between two identical
nanoparticles. In particular, short-range attractions are observed between two
equally charged nanoparticles, even though our model does not include specific
interactions; these attractions are greatly enhanced for anionic nanoparticles
immersed in standard electrolytes where cations are smaller than anions.
Practical implications of some of the presented results are also briefly
discussed. A good accord between the standard Ewald method and the pre-averaged
Ewald approach is attained, despite the fact that the ionic system studied here
is certainly inhomogeneous. In general, good agreement between the liquid theory
approach and MD simulations is also found.
PMID- 22047262
TI - Electronic level alignment at a metal-molecule interface from a short-range
hybrid functional.
AB - Hybrid functionals often exhibit a marked improvement over semi-local functionals
in the description of the electronic structure of organic materials. Because
short-range hybrid functionals, notably the Heyd-Scuseria-Ernzerhof (HSE)
functional, can also describe the electronic structure of metals reasonably well,
it is interesting to examine to which extent they can correctly describe the
electronic structure at metal-organic interfaces. Here, we address this question
by comparing HSE calculations with many-body perturbation theory calculations in
the GW approximation, or with experimental photoemission data, for two
prototypical systems: benzene on graphite and benzene diamine on gold. For both
cases, we find that while HSE yields results that are somewhat closer to
experiment than those of semi-local functionals, the HSE prediction is still
lacking quantitatively by ~1 eV. We show that this quantitative failure arises
because HSE does not correctly capture the fundamental gap of the organic or its
renormalization by the metal. These discrepancies are traced back to missing long
range exchange and correlation components, an explanation which applies to any
conventional or short-range hybrid functional.
PMID- 22047263
TI - Flow-induced control of chemical turbulence.
AB - We report spatiotemporal chaos in the Oregonator model of the Belousov
Zhabotinsky reaction. Spatiotemporal chaos spontaneously develops in a regime,
where the underlying local dynamics show stable limit cycle oscillations
(diffusion-induced turbulence). We show that spatiotemporal chaos can be
suppressed by a unidirectional flow in the system. With increasing flow velocity,
we observe a transition scenario from spatiotemporal chaos via a regime of
travelling waves to a stationary steady state. At large flow velocities, we
recover the known regime of flow distributed oscillations.
PMID- 22047264
TI - Limit of validity of Ostwald's rule of stages in a statistical mechanical model
of crystallization.
AB - We have only rules of thumb with which to predict how a material will
crystallize, chief among which is Ostwald's rule of stages. It states that the
first phase to appear upon transformation of a parent phase is the one closest to
it in free energy. Although sometimes upheld, the rule is without theoretical
foundation and is not universally obeyed, highlighting the need for microscopic
understanding of crystallization controls. Here we study in detail the
crystallization pathways of a prototypical model of patchy particles. The range
of crystallization pathways it exhibits is richer than can be predicted by
Ostwald's rule, but a combination of simulation and analytic theory reveals
clearly how these pathways are selected by microscopic parameters. Our results
suggest strategies for controlling self-assembly pathways in simulation and
experiment.
PMID- 22047265
TI - Computer simulation of bottle-brush polymers with flexible backbone: good solvent
versus theta solvent conditions.
AB - By molecular dynamics simulation of a coarse-grained bead-spring-type model for a
cylindrical molecular brush with a backbone chain of N(b) effective monomers to
which with grafting density sigma side chains with N effective monomers are
tethered, several characteristic length scales are studied for variable solvent
quality. Side chain lengths are in the range 5 <= N <= 40, backbone chain lengths
are in the range 50 <= N(b) <= 200, and we perform a comparison to results for
the bond fluctuation model on the simple cubic lattice (for which much longer
chains are accessible, N(b) <= 1027, and which corresponds to an athermal, very
good, solvent). We obtain linear dimensions of the side chains and the backbone
chain and discuss their N-dependence in terms of power laws and the associated
effective exponents. We show that even at the theta point the side chains are
considerably stretched, their linear dimension depending on the solvent quality
only weakly. Effective persistence lengths are extracted both from the
orientational correlations and from the backbone end-to-end distance; it is shown
that different measures of the persistence length (which would all agree for
Gaussian chains) are not mutually consistent with each other and depend
distinctly both on N(b) and the solvent quality. A brief discussion of pertinent
experiments is given.
PMID- 22047266
TI - Cross-streamline migration of a semiflexible polymer in a pressure driven flow.
AB - Experiments and simulations on single alpha-actin filaments in the Poiseuille
flow through a microchannel show that the center-of-mass probability density
across the channel assumes a bimodal shape as a result of pronounced cross
streamline migration. We reexamine the problem and perform Brownian dynamics
simulations for a bead-spring chain with bending elasticity. Hydrodynamic
interactions between the pointlike beads are taken into account by the two-wall
Green tensor of the Stokes equations. Our simulations reproduce the bimodal
distribution only when hydrodynamic interactions are taken into account.
Numerical results on the orientational order of the end-to-end vector of the
model polymer are also presented together with analytical hard-needle expressions
at zero flow velocity. We derive a Smoluchowski equation for the center-of-mass
distribution and carefully analyze the different contributions to the probability
current that causes the bimodal distribution. As for flexible polymers,
hydrodynamic repulsion explains the depletion at the wall. However, in contrast
to flexible polymers, the deterministic drift current mainly determines migration
away from the centerline and thereby depletion at the center. Diffusional
currents due to a position-dependent diffusivity become less important with
increasing polymer stiffness.
PMID- 22047267
TI - Moment estimation for chemically reacting systems by extended Kalman filtering.
AB - In stochastic models of chemically reacting systems that contain bimolecular
reactions, the dynamics of the moments of order up to n of the species
populations do not form a closed system, in the sense that their time-derivatives
depend on moments of order n + 1. To close the dynamics, the moments of order n +
1 are generally approximated by nonlinear functions of the lower order moments.
If the molecule counts of some of the species have a high probability of becoming
zero, such approximations may lead to imprecise results and stochastic simulation
is the only viable alternative for system analysis. Stochastic simulation can
produce exact realizations of chemically reacting systems, but tends to become
computationally expensive, especially for stiff systems that involve reactions at
different time scales. Further, in some systems, important stochastic events can
be very rare and many simulations are necessary to obtain accurate estimates. The
computational cost of stochastic simulation can then be prohibitively large. In
this paper, we propose a novel method for estimating the moments of chemically
reacting systems. The method is based on closing the moment dynamics by replacing
the moments of order n + 1 by estimates calculated from a small number of
stochastic simulation runs. The resulting stochastic system is then used in an
extended Kalman filter, where estimates of the moments of order up to n, obtained
from the same simulation, serve as outputs of the system. While the initial
motivation for the method was improving over the performance of stochastic
simulation and moment closure methods, we also demonstrate that it can be used in
an experimental setting to estimate moments of species that cannot be measured
directly from time course measurements of the moments of other species.
PMID- 22047268
TI - Determining the DNA stability parameters for the breathing dynamics of
heterogeneous DNA by stochastic optimization.
AB - We suggest that the thermodynamic stability parameters (nearest neighbor stacking
and hydrogen bonding free energies) of double-stranded DNA molecules can be
inferred reliably from time series of the size fluctuations (breathing) of local
denaturation zones (bubbles). On the basis of the reconstructed bubble size
distribution, this is achieved through stochastic optimization of the free
energies in terms of simulated annealing. In particular, it is shown that even
noisy time series allow the identification of the stability parameters at
remarkable accuracy. This method will be useful to obtain the DNA stacking and
hydrogen bonding free energies from single bubble breathing assays rather than
equilibrium data.
PMID- 22047269
TI - A coarse-grain three-site-per-nucleotide model for DNA with explicit ions.
AB - The "three sites per nucleotide" (3SPN) model provides a coarse-grained
representation of nucleic acids for simulation of molecular processes.
Previously, this model has relied on an implicit representation of the
surrounding ionic environment at the level of Debye-Huckel theory. In this work,
we eliminate this limitation and present an explicit representation of ions, both
monovalent and divalent. The coarse-grain ion-ion and ion-phosphate potential
energy functions are inferred from all-atom simulations and parameterized to
reproduce key features of the local structure and organization of ions in bulk
water and in the presence of DNA. The resulting model, 3SPN.1-I, is capable of
reproducing the local structure observed in detailed atomistic simulations, as
well as the experimental melting temperature of DNA for a range of DNA
oligonucleotide lengths, CG-content, Na(+) concentration, and Mg(2+)
concentration.
PMID- 22047270
TI - Comment on "Reactive force fields for surface chemical reactions: a case study
with hydrogen dissociation on Pd surfaces" [J. Chem. Phys. 132, 014704 (2010)].
AB - In a recent paper [Y. Xiao, W. Dong, and H. F. Busnengo, J. Chem. Phys. 132,
014704 (2010)], two of us (Y.X. and W.D.) and H. F. Busnengo reported the
parameterization of some reactive force fields (RFF) for describing the
dissociative adsorption of H2 on Pd surfaces. They obtained a sufficiently
accurate RFF by using the reactive bond order (REBO) formalism of Brenner and
showed that the simpler RFF based on the second moment approximation (SMA) failed
in giving reliable results. It was concluded that the failure is due to the
oversimplified expressions of RFF based on SMA and hence the lack of necessary
flexibility. The results of our more recent investigation show that this
conclusion needs to be corrected. A more suitable choice of the parameterization
conditions allows, in fact, for obtaining a reliable RFF from SMA also.
PMID- 22047271
TI - Comment on "Study of dielectric relaxations of anhydrous trehalose and maltose
glasses" [J. Chem. Phys. 134, 014508 (2011)].
AB - Very recently Kwon et al. [H.-J. Kwon, J.-A. Seo, H. K. Kim, and Y. H. Hwang, J.
Chem. Phys. 134, 014508 (2011)] published an article on the study of dielectric
relaxation in trehalose and maltose glasses. They carried out broadband
dielectric measurements at very wide range of temperatures covering supercooled
liquid as well as glassy state of both saccharides. It is worth to mention that
authors have also applied a new method for obtaining anhydrous glasses of
trehalose and maltose that enables avoiding their caramelization. Four relaxation
processes were identified in dielectric spectra of both saccharides. The slower
one was identified as structural relaxation process the next one, not observed by
the others, was assigned as Johari-Goldstein (JG) beta-relaxation, while the last
two secondary modes were of the same nature as found by Kaminski et al. [K.
Kaminski, E. Kaminska, P. Wlodarczyk, S. Pawlus, D. Kimla, A. Kasprzycka, M.
Paluch, J. Ziolo, W. Szeja, and K. L. Ngai, J. Phys. Chem. B 112, 12816 (2008)].
In this comment we show that the authors mistakenly assigned the slowest
relaxation process as structural mode of disaccharides. We have proven that this
relaxation process is an effect of formation of thin layer of air or water
between plate of capacitor and sample. The same effect can be observed if plates
of capacitor are oxidized. Thus, we concluded that their slowest mode is
connected to the dc conduction process while their beta JG process is primary
relaxation of trehalose and maltose.
PMID- 22047273
TI - Invited review article: Interferometric gravity wave detectors.
AB - A direct detection of gravitational waves is still lacking today. A network of
several earthbound interferometric detectors is currently operating with a
continuously improving sensitivity. The window of interest for observation has a
lower cut off in the frequency domain below some tens of hertz, determined by the
effect of seismic motion. For larger frequencies, the sensitivity is limited by
thermal effects below few hundreds of hertz and by the quantum nature of light
above that value. Each of these sources of noise pose a big technological
challenge to experimentalists, and there are big expectations for the next
generation of detectors. A reduction of thermal effects by at least one order of
magnitude will be obtained with new and carefully designed materials. At that
point the quantum nature of light will become an issue, and the use of quantum
non-demolition techniques will become mandatory. In this review, we discuss
interferometric detection of gravitational waves from an instrumental point of
view. We try to address conceptually important issues with an audience of non
experts in mind. A particular emphasis is given to the description of the current
limitations and to the perspectives of beating them.
PMID- 22047274
TI - A sample holder for soft x-ray absorption spectroscopy of liquids in transmission
mode.
AB - A novel sample holder for soft x-ray absorption spectroscopy of liquids in
transmission mode based on sample cells with x-ray transparent silicon nitride
membranes is introduced. The sample holder allows for a reliable preparation of
ultrathin liquid films with an adjustable thickness in the nm-MUm range. This
enables measurements of high quality x-ray absorption spectra of liquids in
transmission mode, as will be shown for the example of liquid H(2)O, aqueous
solutions of 3d-transition metal ions and alcohol-water mixtures. The fine
structure of the x-ray absorption spectra is not affected by the sample
thickness. No effects of the silicon nitride membranes were observed in the
spectra. It is shown how an inhomogeneous thickness of the sample affects the
spectra and how this can be avoided.
PMID- 22047275
TI - A portable fluorescence detector for fast ultra trace detection of explosive
vapors.
AB - This paper developed a portable detector based on a specific material-based
fluorescent sensing film for an ultra trace detection of explosives, such as
2,4,6-trinitrotoluene (TNT) or its derivate 2,4-dinitrotoluene (DNT), in ambient
air or on objects tainted by explosives. The fluorescent sensing films are based
on single-layer chemistry and the signal amplification effect of conjugated
polymers, which exhibited higher sensitivity and shorter response time to TNT or
DNT at their vapor pressures. Due to application of the light emitting diode and
the solid state photomultiplier and the cross-correlation-based circuit design
technology, the device has the advantages of low-power, low-cost, small size, and
an improved signal to noise ratio. The results of the experiments showed that the
detector can real-time detect and identify of explosive vapors at extremely low
levels; it is suitable for the identification of suspect luggage, forensic
analyses, or battlefields clearing.
PMID- 22047276
TI - Field-programmable gate array based locking circuit for external cavity diode
laser frequency stabilization.
AB - We present a locking circuit for external cavity diode lasers implemented on a
field-programmable gate array (FPGA). The main advantages over traditional non
FPGA-based locking circuits are rapid reconfigurability without any soldering and
a friendly user interface. We characterize the lock quality by measuring the
linewidth of a locked laser using electromagnetically induced transparency in a
Rb vapor cell.
PMID- 22047277
TI - Fully automated spatially resolved reflectance spectrometer for the determination
of the absorption and scattering in turbid media.
AB - We describe a fully automated setup which is based on measurements of the
spatially resolved reflectance for the determination of the reduced scattering
and absorption coefficients in semi-infinite turbid media. The sample is
illuminated with a xenon light source in combination with a monochromator
enabling the scan of the wavelength from 450 nm to 950 nm. Reflected light from
the sample is detected with a CCD camera providing a high spatial resolution. The
essential steps for signal processing including, e.g., the consideration of the
optical transfer function and the correct treatment of the background
subtraction, are presented. The solutions of the diffusion theory and of the
radiative transfer theory are investigated regarding the exact detection and
illumination geometry. Systematic errors caused by using the different theories
for fitting the optical parameters are characterized. The system was validated
using liquid phantoms which contain Intralipid 20% and ink, and the measurement
range of the system is specified. Further, we carefully characterized the optical
properties of Intralipid 20% in the wavelength range between 450 nm and 950 nm.
PMID- 22047278
TI - A magnetic-bottle multi-electron-ion coincidence spectrometer.
AB - A novel multi-electron-ion coincidence spectrometer developed on the basis of a
1.5 m-long magnetic-bottle electron spectrometer is presented. Electrons are
guided by an inhomogeneous magnetic field to a detector at the end of the flight
tube, while a set of optics is used to extract counterpart ions to the same
detector, by a pulsed inhomogeneous electric field. This setup allows ion
detection with high mass resolution, without impairing the high collection
efficiency for electrons. The performance of the coincidence spectrometer was
tested with double ionization of carbon disulfide, CS(2) -> CS(2)(2+) + e(-) + e(
), in ultrashort intense laser fields (2.8 * 10(13) W/cm(2), 280 fs, 1030 nm) to
clarify the electron correlation below the rescattering threshold.
PMID- 22047279
TI - Characterization of near-terahertz complementary metal-oxide semiconductor
circuits using a Fourier-transform interferometer.
AB - Optical methods for measuring of the emission spectra of oscillator circuits
operating in the 400-600 GHz range are described. The emitted power from patch
antennas included in the circuits is measured by placing the circuit in the
source chamber of a Fourier-transform interferometric spectrometer. The results
show that this optical technique is useful for measuring circuits pushing the
frontier in operating frequency. The technique also allows the characterization
of the circuit by measuring the power radiated in the fundamental and in the
harmonics. This capability is useful for oscillator architectures designed to
cancel the fundamental and use higher harmonics. The radiated power was measured
using two techniques: direct measurement of the power by placing the device in
front of a bolometer of known responsivity, and by comparison to the estimated
power from blackbody sources. The latter technique showed that these circuits
have higher emission than blackbody sources at the operating frequencies, and,
therefore, offer potential spectroscopy applications.
PMID- 22047280
TI - Simultaneous time and wavelength resolved spectroscopy under two-colour near
infrared and terahertz excitation.
AB - Time and wavelength resolved spectroscopy requires optical sources emitting very
short pulses and a fast detection mechanism capable of measuring the evolution of
the output spectrum as a function of time. We use table-top Ti:sapphire lasers
and a free-electron laser (FEL) emitting ps pulses as excitation sources and a
streak camera coupled to a spectrometer for detection. One of the major aspects
of this setup is the synchronization of pulses from the two lasers which we
describe in detail. Optical properties of the FEL pulses are studied by
autocorrelation and electro-optic sampling measurements. We discuss the
advantages of using this setup to perform photoluminescence quenching in
semiconductor quantum wells and quantum dots. Carrier redistribution due to
pulsed excitation in these heterostructures can be investigated directly.
Sideband generation in quantum wells is also studied where the intense FEL pulses
facilitate the detection of the otherwise weak nonlinear effect.
PMID- 22047281
TI - A line-imaging velocity interferometer technique for shock diagnostics without x
ray preheat limitation.
AB - A study was conducted with a line-imaging velocity interferometer on sandwich
targets at the Shen Guang-III prototype laser facility in China, with the goal of
eliminating the preheat effect. A sandwich target structure was used to reduce
the x-ray preheat limitation (radiation temperature ~170 eV) in a radiative drive
shock experiment. With a thick ablator, the preheat effect appeared before the
shock arrived at the window. After adding a shield layer of high-Z material on
the ablator, x-rays which penetrated the ablator were so weak that the blank-out
effect could not be measured. This experiment indicates that the sandwich target
may provide a valuable technique in experiments such as equation of state and
shock timing for inertial confinement fusion studies.
PMID- 22047282
TI - Research on the fiber Bragg grating sensor for the shock stress measurement.
AB - A fiber Bragg grating (FBG) sensor with an unbalanced Mach-Zehnder fiber
interferometer for the shock stress measurement is proposed and demonstrated. An
analysis relationship between the shock stress and the central reflection
wavelength shift of the FBG is firstly derived. In this sensor, the optical path
difference of the unbalanced Mach-Zehnder fiber interferometer is ~3.1 mm and the
length of the FBG is 2 mm. An arctangent function reduction method, which can
avoid sine function's insensitive zone where the shock stress measurement has a
reduced accuracy, is presented. A shock stress measurement of water driven by one
stage gun (up to 1.4 GPa), with good theoretical accuracy (~10%), is launched.
PMID- 22047283
TI - Laser-locked, continuously tunable high resolution cavity ring-down spectrometer.
AB - A continuous-wave cavity ring-down spectrometer with sub-MHz precision has been
built using the sideband of a frequency stabilized laser as the tunable light
source. The sideband is produced by passing the carrier laser beam through an
electro-optic modulator (EOM) and then selected by a short etalon on resonance.
The carrier laser frequency is locked to a longitude mode of a thermo-stabilized
Fabry-Perot interferometer (FPI) with a long-term absolute frequency stability of
0.2 MHz (5 * 10(-10)). Broad and precise spectral scanning is accomplished,
respectively, by selecting a different longitudinal mode of the FPI and by tuning
the radio-frequency driving the EOM. The air broadened water absorption line at
12,321 cm(-1) was studied to test the performance of the spectrometer.
PMID- 22047284
TI - Combined optical and acoustical method for determination of thickness and
porosity of transparent organic layers below the ultra-thin film limit.
AB - Analysis techniques are needed to determine the quantity and structure of
materials composing an organic layer that is below an ultra-thin film limit and
in a liquid environment. Neither optical nor acoustical techniques can
independently distinguish between thickness and porosity of ultra-thin films due
to parameter correlation. A combined optical and acoustical approach yields
sufficient information to determine both thickness and porosity. We describe
application of the combinatorial approach to measure single or multiple organic
layers when the total layer thickness is small compared to the wavelength of the
probing light. The instrumental setup allows for simultaneous in situ
spectroscopic ellipsometry and quartz crystal microbalance dynamic measurements,
and it is combined with a multiple-inlet fluid control system for different
liquid solutions to be introduced during experiments. A virtual separation
approach is implemented into our analysis scheme, differentiated by whether or
not the organic adsorbate and liquid ambient densities are equal. The analysis
scheme requires that the film be assumed transparent and rigid (non
viscoelastic). We present and discuss applications of our approach to studies of
organic surfactant adsorption, self-assembled monolayer chemisorption, and
multiple-layer target DNA sensor preparation and performance testing.
PMID- 22047285
TI - Detection of atomic and molecular mega-electron-volt projectiles using an x-ray
charged coupled device camera.
AB - We show that an x-ray charge coupled device (CCD) may be used as a particle
detector for atomic and molecular mega-electron-volt (MeV) projectiles of around
a few hundred keV per atomic mass unit. For atomic species, spectroscopic
properties in kinetic energy measurements (i.e., linearity and energy resolution)
are found to be close to those currently obtained with implanted or surface
barrier silicon particle detectors. For molecular species, in order to increase
the maximum kinetic energy detection limit, we propose to put a thin foil in
front of the CCD. This foil breaks up the molecules into atoms and spreads the
charges over many CCD pixels and therefore avoiding saturation effects. This
opens new perspectives in high velocity molecular dissociation studies with
accelerator facilities.
PMID- 22047286
TI - Efficient spin resolved spectroscopy observation machine at Hiroshima Synchrotron
Radiation Center.
AB - Highly efficient spin- and angle-resolved photoelectron spectrometer named
ESPRESSO (Efficient SPin REsolved SpectroScopy Observation) machine has been
developed at the beamline BL-9B in Hiroshima Synchrotron Radiation Center.
Combination of high-resolution hemispherical electron analyzer and the high
efficient spin detector based on very low energy electron diffraction by the
ferromagnetic target makes the high-energy resolution and angular resolution
compatible with spin- and angle-resolved photoemission (SARPES) measurement. 7.5
meV in energy and +/-0.18 degrees in angular resolution have been achieved with
spin resolution. The ESPRESSO machine, combination of quick energy-band
dispersion measurement and Fermi surface mapping by two-dimensional electron
detector for the spin integrated ARPES and the high-efficient spin analysis by
the efficient spin detector realizes the comprehensive investigation of spin
electronic structure of materials.
PMID- 22047287
TI - The response of CR-39 nuclear track detector to 1-9 MeV protons.
AB - The response of CR-39 nuclear track detector (TasTrak((r))) to protons in the
energy range of 0.92-9.28 MeV has been studied. Previous studies of the CR-39
response to protons have been extended by examining the piece-to-piece
variability in addition to the effects of etch time and etchant temperature; it
is shown that the shape of the CR-39 response curve to protons can vary from
piece-to-piece. Effects due to the age of CR-39 have also been studied using 5.5
MeV alpha particles over a 5-year period. Track diameters were found to degrade
with the age of the CR-39 itself rather than the age of the tracks, consistent
with previous studies utilizing different CR-39 over shorter time periods.
PMID- 22047288
TI - Edge and core Thomson scattering systems and their calibration on the ASDEX
Upgrade tokamak.
AB - A new 10 channel Thomson scattering (TS) system was installed on the ASDEX
Upgrade tokamak to measure radial profiles of electron density and temperature at
the plasma edge with high radial resolution. Together with the already existing
TS system, which is now used for the core plasma, electron density and
temperature profiles extending from the edge to the core are now obtained in a
single discharge. The TS systems are relatively calibrated by an optical
parametric oscillator.
PMID- 22047289
TI - Techniques for the measurement of disruption halo currents in the National
Spherical Torus Experiment.
AB - This paper describes techniques for measuring halo currents, and their associated
toroidal peaking, in the National Spherical Torus Experiments [M. Ono et al.,
Nucl. Fusion 40, 557 (2000)]. The measurements are based on three techniques: (1)
measurement of the toroidal field created by the poloidal halo current, either
with segmented Rogowski coils or discrete toroidal field sensors, (2) the direct
measurement of halo currents into specially instrument tiles, and (3) small
Rogowski coils placed on the mechanical supports of in-vessel components. For the
segmented Rogowski coils and discrete toroidal field detectors, it is shown that
the toroidal peaking factor inferred from the data is significantly less than the
peaking factor of the underlying halo current distribution, and a simple model is
developed to relate the two. For the array of discrete toroidal field detectors
and small Rogowski sensors, the compensation steps that are used to isolate the
halo current signal are described. The electrical and mechanical design of
compact under-tile resistive shunts and mini-Rogowski coils is described. Example
data from the various systems are shown.
PMID- 22047290
TI - Development of a compact permanent magnet helicon plasma source for ion beam
bioengineering.
AB - A compact helicon plasma source was developed as a millimeter-sized ion source
for ion beam bioengineering. By employing a stacked arrangement of annular-shaped
permanent magnets, a uniform axial magnetic flux density up to 2.8 kG was
obtained. A cost effective 118 MHz RF generator was built for adjusting forward
output power from 0 to 40 W. The load impedance and matching network were then
analyzed. A single loop antenna and circuit matching elements were placed on a
compact printed circuit board for 50 Omega impedance matching. A plasma density
up to 1.1 * 10(12) cm(-3) in the 10 mm diameter tube under the magnetic flux
density was achieved with 35 W applied RF power.
PMID- 22047291
TI - Deconvolution of Stark broadened spectra for multi-point density measurements in
a flow Z-pinch.
AB - Stark broadened emission spectra, once separated from other broadening effects,
provide a convenient non-perturbing means of making plasma density measurements.
A deconvolution technique has been developed to measure plasma densities in the
ZaP flow Z-pinch experiment. The ZaP experiment uses sheared flow to mitigate MHD
instabilities. The pinches exhibit Stark broadened emission spectra, which are
captured at 20 locations using a multi-chord spectroscopic system. Spectra that
are time- and chord-integrated are well approximated by a Voigt function. The
proposed method simultaneously resolves plasma electron density and ion
temperature by deconvolving the spectral Voigt profile into constituent
functions: a Gaussian function associated with instrument effects and Doppler
broadening by temperature; and a Lorentzian function associated with Stark
broadening by electron density. The method uses analytic Fourier transforms of
the constituent functions to fit the Voigt profile in the Fourier domain. The
method is discussed and compared to a basic least-squares fit. The Fourier
transform fitting routine requires fewer fitting parameters and shows promise in
being less susceptible to instrumental noise and to contamination from
neighboring spectral lines. The method is evaluated and tested using simulated
lines and is applied to experimental data for the 229.69 nm C III line from
multiple chords to determine plasma density and temperature across the diameter
of the pinch. These measurements are used to gain a better understanding of Z
pinch equilibria.
PMID- 22047292
TI - Design and use of an Elsasser probe for analysis of Alfven wave fields according
to wave direction.
AB - We have designed an electric and magnetic field probe which simultaneously
measure both quantities in the directions perpendicular to the background
magnetic field for application to Alfven wave experiments in the Large Plasma
Device at UCLA. This new probe allows for the projection of measured wave fields
onto generalized Elsasser variables. Experiments were conducted in a singly
ionized He plasma at 1850 G in which propagation of Alfven waves was observed
using this new probe. We demonstrate that a clear separation of transmitted and
reflected signals and determination of Poynting flux and Elsasser variables can
be achieved.
PMID- 22047293
TI - Application of an impedance matching transformer to a plasma focus.
AB - A plasma focus was constructed using an impedance matching transformer to improve
power transfer between the pulse power and the dynamic plasma load. The system
relied on two switches and twelve transformer cores to produce a 100 kA pulse in
short circuit on the secondary at 27 kV on the primary with 110 J stored. With
the two transformer systems in parallel, the Thevenin equivalent circuit
parameters on the secondary side of the driver are: C = 10.9 MUF, V(0) = 4.5 kV,
L = 17 nH, and R = 5 mOmega. An equivalent direct drive circuit would require a
large number of switches in parallel, to achieve the same Thevenin equivalent.
The benefits of this approach are replacement of consumable switches with non
consumable transformer cores, reduction of the driver inductance and resistance
as viewed by the dynamic load, and reduction of the stored energy to produce a
given peak current. The system is designed to operate at 100 Hz, so minimizing
the stored energy results in less load on the thermal management system. When
operated at 1 Hz, the neutron yield from the transformer matched plasma focus was
similar to the neutron yield from a conventional (directly driven) plasma focus
at the same peak current.
PMID- 22047294
TI - Detection efficiency vs. cathode and anode separation in cylindrical vacuum
photodiodes used for measuring x-rays from plasma focus device.
AB - A qualitative study on the performance of cylindrical vacuum photodiodes (VPDs)
for x-ray detection in plasma focus device has been carried out. Various
parameters of VPD such as electrode's diameter, electrode's separation, and its
sensitivity are experimentally tested in plasma focus environment. For the first
time it is found experimentally that the electrode-separation in the lateral
direction of the two coaxial electrodes of cylindrical VPD also plays an
important role to increase the efficiency of the detector. The efficiency is
found to be highest for the detector with smaller cathode-anode lateral gap (1.5
mm) with smaller photo cathode diameter (10 mm). A comparison between our VPD
with PIN (BPX-65) diode as an x-ray detector has also been made.
PMID- 22047295
TI - Time-frequency analysis for microwave reflectometry data processing in the HL-2A
tokamak.
AB - The Choi-Williams distribution (CWD) technique is introduced as a time-frequency
tool for processing data measured from the new developed homodyne and the fixed
frequency reflectometry in the HL-2A tokamak. The comparison between spectrogram
and CWD for the simulated signal is presented. It indicates that the CWD can
greatly improve the representation of the time-frequency content of the multi
components signal. Its effectiveness is demonstrated through two applications in
HL-2A, which are the extraction of beat frequencies from the frequency modulated
continuous wave reflectometry (FM-CW) and the characterizing of the fluctuations.
The density profile inversed from the group delay of the FM-CW and the density
fluctuations deduced from the fixed-frequency reflectometry would be more
reliable and accurate by using the CWD technique.
PMID- 22047296
TI - Properties of a capillary discharge-produced argon plasma waveguide for shorter
wavelength source application.
AB - We report the operation of a discharge-produced argon (Ar) plasma waveguide in an
alumina (Al(2)O(3)) capillary to guide a 10(16)-W/cm(2) ultrashort laser pulse
for shorter wavelength light sources at high repetition rate operation. The
electron density in the plasma channel was measured to be 1 * 10(18) cm(-3).
Modeling with a one-dimensional magnetrohydrodynamic code was used to evaluate
the degree of ionization of Ar in the preformed plasma channel. The observed
spectrum of the laser pulse after propagation in the argon plasma waveguide was
not modified and was well reproduced by a particle in cell simulation.
PMID- 22047297
TI - Field programmable gate array based reconfigurable scanning probe/optical
microscope.
AB - The increasing popularity of nanometrology and nanospectroscopy has pushed
researchers to develop complex new analytical systems. This paper describes the
development of a platform on which to build a microscopy tool that will allow for
flexibility of customization to suit research needs. The novelty of the described
system lies in its versatility of capabilities. So far, one version of this
microscope has allowed for successful near-field and far-field fluorescence
imaging with single molecule detection sensitivity. This system is easily adapted
for reflection, polarization (Kerr magneto-optical (MO)), Raman, super-resolution
techniques, and other novel scanning probe imaging and spectroscopic designs.
While collecting a variety of forms of optical images, the system can
simultaneously monitor topographic information of a sample with an integrated
tuning fork based shear force system. The instrument has the ability to image at
room temperature and atmospheric pressure or under liquid. The core of the design
is a field programmable gate array (FPGA) data acquisition card and a single, low
cost computer to control the microscope with analog control circuitry using off
the-shelf available components. A detailed description of electronics, mechanical
requirements, and software algorithms as well as examples of some different forms
of the microscope developed so far are discussed.
PMID- 22047298
TI - A compact sub-Kelvin ultrahigh vacuum scanning tunneling microscope with high
energy resolution and high stability.
AB - We designed a scanning tunneling microscope working at sub-Kelvin temperatures in
ultrahigh vacuum (UHV) in order to study the magnetic properties on the
nanoscale. An entirely homebuilt three-stage cryostat is used to cool down the
microscope head. The first stage is cooled with liquid nitrogen, the second stage
with liquid (4)He. The third stage uses a closed-cycle Joule-Thomson refrigerator
of a cooling power of 1 mW. A base temperature of 930 mK at the microscope head
was achieved using expansion of (4)He, which can be reduced to ~400 mK when using
(3)He. The cryostat has a low liquid helium consumption of only 38 ml/h and
standing times of up to 280 h. The fast cooling down of the samples (3 h)
guarantees high sample throughput. Test experiments with a superconducting tip
show a high energy resolution of 0.3 meV when performing scanning tunneling
spectroscopy. The vertical stability of the tunnel junction is well below 1 pm
(peak to peak) and the electric noise floor of tunneling current is about
6fA/?Hz. Atomic resolution with a tunneling current of 1 pA and 1 mV was achieved
on Au(111). The lateral drift of the microscope at stable temperature is below 20
pm/h. A superconducting spilt-coil magnet allows to apply an out-of-plane
magnetic field of up to 3 T at the sample surface. The flux vortices of a Nb(110)
sample were clearly resolved in a map of differential conductance at 1.1 K and a
magnetic field of 0.21 T. The setup is designed for in situ preparation of tip
and samples under UHV condition.
PMID- 22047299
TI - Vector potential photoelectron microscopy.
AB - A new class of electron microscope has been developed for the chemical
microanalysis of a wide range of real world samples using photoelectron
spectroscopy. Highly structured, three-dimensional samples, such as fiber mats
and fracture surfaces can be imaged, as well as insulators and magnetic
materials. The new microscope uses the vector potential field from a solenoid
magnet as a spatial reference for imaging. A prototype instrument has
demonstrated imaging of uncoated silk, magnetic steel wool, and micron-sized
single strand tungsten wires.
PMID- 22047300
TI - Measurement sensitivity improvement in tapping-mode atomic force microscopy
through bi-harmonic drive signal.
AB - This article presents a novel method to improve the measurement sensitivity and
reduce impact forces in tapping-mode atomic force microscopy by reshaping the tip
trajectory. A tapping drive signal composed of two harmonics is used to generate
an oscillating trajectory with a broader valley compared to the typical
sinusoidal trajectory. The wide broad valley reduces the velocity of the tip in
the vicinity of the sample and allots a greater portion of each period in the
vicinity of the sample. Numerical simulations show that this results in decreased
impact force and increased sensitivity of the cantilever oscillation to changes
in tip-sample offset. Experimental results demonstrate an increase in image
sharpness and decrease in tip wear using the bi-harmonic driving signal.
PMID- 22047301
TI - A simple approach to neutral atom microscopy.
AB - Scanning surfaces using a beam of noncharged atoms or molecules allows for
especially nondestructive and low-energy surface imaging, with the potential to
obtain new information about surfaces that cannot be easily obtained otherwise.
We have developed a new approach, operating with the sample at a close working
distance from an aperture, the need for optics to focus the beam is obviated.
Compared to more complex approaches, the theoretical performance has no other
disadvantage than the short working distance. Resolution of 1.5 MUm has been
achieved, and submicron resolution appears to be practical. Construction of the
microscope and results are presented, including first images done in reflection
mode, theory for optimization of the design and avenues for future improvement.
PMID- 22047302
TI - Calibration method of tilt and azimuth angles for alignment of TEM tomographic
tilt series.
AB - This paper describes the calibration method of the tilt and azimuth angles of
specimen using a digital protractor and a laser autocollimator for alignment of
electron tomography. It also suggests an easy method to check whether the
specimen is tilted by 180.0 degrees , and whether the azimuth angle is 0.0
degrees ; the method involves the use of two images of a rod-shaped specimen
collected before and after a 180.0 degrees tilt. The method is based on the
assumption that these images are symmetric about the tilt axis when the azimuth
angle is 0.0 degrees . In addition, we used an experiment to demonstrate the
effect of the incorrect angles on reconstructed images and simulated the image
quality against distance away from tilt axis.
PMID- 22047303
TI - A method to track rotational motion for use in single-molecule biophysics.
AB - The double helical nature of DNA links many cellular processes such as DNA
replication, transcription, and repair to rotational motion and the accumulation
of torsional strain. Magnetic tweezers (MTs) are a single-molecule technique that
enables the application of precisely calibrated stretching forces to nucleic acid
tethers and to control their rotational motion. However, conventional magnetic
tweezers do not directly monitor rotation or measure torque. Here, we describe a
method to directly measure rotational motion of particles in MT. The method
relies on attaching small, non-magnetic beads to the magnetic beads to act as
fiducial markers for rotational tracking. CCD images of the beads are analyzed
with a tracking algorithm specifically designed to minimize crosstalk between
translational and rotational motion: first, the in-plane center position of the
magnetic bead is determined with a kernel-based tracker, while subsequently the
height and rotation angle of the bead are determined via correlation-based
algorithms. Evaluation of the tracking algorithm using both simulated images and
recorded images of surface-immobilized beads demonstrates a rotational resolution
of 0.1 degrees , while maintaining a translational resolution of 1-2 nm. Example
traces of the rotational fluctuations exhibited by DNA-tethered beads confined in
magnetic potentials of varying stiffness demonstrate the robustness of the method
and the potential for simultaneous tracking of multiple beads. Our rotation
tracking algorithm enables the extension of MTs to magnetic torque tweezers (MTT)
to directly measure the torque in single molecules. In addition, we envision uses
of the algorithm in a range of biophysical measurements, including further
extensions of MT, tethered particle motion, and optical trapping measurements.
PMID- 22047304
TI - Use of scanning probe microscopy to study the evolution of nanometer sized liquid
structures.
AB - The evolution of the profile of nanometer sized water drops on a mica surface has
been studied through hydration scanning probe microscopy. A time range from a few
seconds down to a fraction of millisecond after the formation of the drop has
been explored. This high time resolution has been obtained by sampling a series
of statistically equivalent drops. This approach also avoids any probe
interference during the drop evolution process.
PMID- 22047305
TI - Magnifying lens for 800 MeV proton radiography.
AB - This article describes the design and performance of a magnifying magnetic-lens
system designed, built, and commissioned at the Los Alamos National Laboratory
(LANL) for 800 MeV flash proton radiography. The technique of flash proton
radiography has been developed at LANL to study material properties under dynamic
loading conditions through the analysis of time sequences of proton radiographs.
The requirements of this growing experimental program have resulted in the need
for improvements in spatial radiographic resolution. To meet these needs, a new
magnetic lens system, consisting of four permanent magnet quadrupoles, has been
developed. This new lens system was designed to reduce the second order chromatic
aberrations, the dominant source of image blur in 800 MeV proton radiography, as
well as magnifying the image to reduce the blur contribution from the detector
and camera systems. The recently commissioned lens system performed as designed,
providing nearly a factor of three improvement in radiographic resolution.
PMID- 22047306
TI - Magneto-optical Kerr effect susceptometer for the analysis of magnetic domain
wall dynamics.
AB - Domain wall dynamics in thin magnetic films with perpendicular and in-plane
anisotropy is studied using a novel magneto-optical Kerr effect susceptometery
method. The method allows for measurements of domain wall motion under ac field
excitation and the analysis of dynamic modes as a function of driving frequency
and magnetic field amplitude. Domain wall dynamics in the perpendicular
anisotropy system, a Co/Pt multilayer, is characterized by thermally activated
creep motion. For this dynamic mode, a polydispersivity exponent of beta = 0.50
+/- 0.03 is derived at small excitation energy, which is in excellent agreement
with theoretical models. The dynamics of the other system, a Co wire with
transverse uniaxial anisotropy, is dominated by viscous slide motion in a regular
magnetic stripe pattern. Analytical expressions are derived for this magnetic
configuration and by using these expressions, accurate values for the depinning
field and the domain wall mobility are extracted from the susceptibility
measurements.
PMID- 22047307
TI - The extended surface forces apparatus. IV. Precision static pressure control.
AB - We report on design and performance of an extended surface forces apparatus
(eSFA) built into a pressurized system. The aim of this instrument is to provide
control over static pressure and temperature to facilitate direct surface force
experiments in equilibrium with fluids at different loci of their phase diagram.
We built an autoclave that can bear a miniature eSFA. To avoid mechanical or
electrical feedtroughs the miniature apparatus uses an external surface coarse
approach stage under ambient conditions. The surface separation is thus pre
adjusted to approximately ~3 MUm before sliding the apparatus into the autoclave.
Inside the autoclave, the surface separation can be further controlled with a
magnetic drive at sub-Angstrom precision over a 14 MUm range. The autoclave
pressure can then be set and maintained between 20 mbar and 170 bars with few
mbar precision. The autoclave is connected to a specially designed pressurization
system to precondition the fluids. The temperature can be controlled between -20
and 60 degrees C with few mK precision. We demonstrate the operation of the
instrument in the case of gaseous or liquid carbon dioxide. Thanks to a
consequent decoupling of the eSFA mechanical loop from the autoclave structure,
the obtained measurement stability and reproducibility, at elevated pressures, is
comparable to the one established for the conventional eSFA, operated under
ambient conditions.
PMID- 22047308
TI - Alternating-current induced thermal fatigue of gold interconnects with nanometer
scale thickness and width.
AB - With dramatic reduction in sizes of microelectronic devices, the characteristic
width and thickness of interconnects in large-scale integrated circuits have
reached nanometer scale. Thermal fatigue damage of so small interconnects has
attracted more and more attentions. In this work, thermal fatigue of Au
interconnects, 35 nm thick and 0.1-5 MUm wide, is investigated by applying
various alternating current densities to generate cycling temperature and strain
in them. A multi-probe measuring system is installed in a scanning electron
microscope and a probe-type temperature sensor is for the first time introduced
into the system for real-time measuring the temperatures on the pads of the
tested interconnects. A one-dimensional heat conduction equation, which uses
measured temperatures on the pads as boundary conditions and includes a term of
heat dissipation through the interface between the interconnect and the oxidized
silicon substrate, is proposed to calculate the time-resolved temperature
distribution along the Au interconnects. The measured fatigue lifetimes are
presented versus current density and thermal cyclic strain, and the results show
that narrower Au lines are more reliable. The failure mechanism of those Au
interconnects differs from what is observed in thick interconnects with
relatively larger grain size. Topography change caused by localized plasticity on
the less-constrained surfaces of the interconnects have not been observed.
Instead, grain growing and reorienting due to local temperature varying appear,
and grain boundary migration and mergence take place during high temperature
fatigue in such thin and narrow interconnects. These results seem to reflect a
strain-induced boundary migration mechanism, and the damage morphology also
suggests that fatigue of the interconnects with decreased grain size and film
thickness is controlled by diffusive mechanisms and interface properties rather
than by dislocation glide. Open circuit eventually took place by melting at a
region of severely damage cross-sectional area with the grain growing and
reorienting.
PMID- 22047309
TI - Quantitative calibration of radiofrequency NMR Stark effects.
AB - Nuclear magnetic resonance (NMR) Stark responses can occur in quadrupolar nuclei
for an electric field oscillating at twice the usual NMR frequency (2omega(0)).
Calibration of responses to an applied E field is needed to establish nuclear
spins as probes of native E fields within material and molecular systems. We
present an improved approach and apparatus for accurate measurement of
quadrupolar Stark effects. Updated values of C(14) (the response parameter in
cubic crystals) were obtained for both (69)Ga and (75)As in GaAs. Keys to
improvement include a modified implementation of voltage dividers to assess the
2omega(0) amplitude, |E|, and the stabilization of divider response by reduction
of stray couplings in 2omega(0) circuitry. Finally, accuracy was enhanced by
filtering sets of |E| through a linear response function that we established for
the radiofrequency amplifier. Our approach is verified by two types of spectral
results. Steady-state 2omega(0) excitation to presaturate NMR spectra yielded
C(14) = (2.59 +/- 0.06) * 10(12) m(-1) for (69)Ga at room-temperature and 14.1 T.
For (75)As, we obtained (3.1 +/- 0.1) * 10(12) m(-1). Both values reconcile with
earlier results from 77 K and below 1 T, whereas current experiments are at room
temperature and 14.1 T. Finally, we present results where few-microsecond pulses
of the 2omega(0) field induced small (tens of Hz) changes in high-resolution NMR
line shapes. There too, spectra collected vs |E| agree with the model for
response, further establishing the validity of our protocols to specify |E|.
PMID- 22047310
TI - High sensitivity detection of radio-frequency modulated magnetic moment in
semiconductors.
AB - An experimental setup has been realized to measure weak magnetic moments which
can be modulated at radio frequencies (~1-5 MHz). Using an optimized radio
frequency (RF) pickup coil and lock-in amplifier, an experimental sensitivity of
10(-15) Am(2) corresponding to 10(-18) emu has been demonstrated with a 1 s time
constant. The detection limit at room temperature is 9.3 * 10(-16) Am(2)/?Hz
limited by Johnson noise of the coil. The setup has been used to directly measure
the magnetic moment due to a small number (~7 * 10(8)) of spin polarized
electrons generated by polarization modulated optical radiation in GaAs and Ge.
PMID- 22047311
TI - Characteristic impedance and capacitance analysis of Blumlein type pulse forming
line of accelerator based on tape helix.
AB - In this paper, the electromagnetic dispersion theory and the classic telegraph
equations were combined to calculate the important parameters of the helical
Blumlein pulse forming line (BPFL) of accelerator based on tape helix. In the
work band of the BPFL at several hundred ns range, electromagnetic dispersion
characteristics were almost determined by the zeroth harmonic. In order to
testify the dispersion theory of BPFL in this paper, filling dielectrics, such as
de-ionized water, transformer oil, and air were employed in the helical BPFL,
respectively. Parameters such as capacitance, inductance, characteristic
impedance, and pulse duration of the BPFL were calculated. Effects of dispersion
on these parameters were analyzed. Circuit simulation and electromagnetic
simulation were carried out to prove these parameters of BPFL filled with these
three kinds of dielectrics, respectively. The accelerator system was set up, and
experimental results also corresponded to the theoretical calculations. The
average theoretical errors of impedances and pulse durations were 3.5% and 3.4%,
respectively, which proved the electromagnetic dispersion analyses in this paper.
PMID- 22047312
TI - Megavolt range voltage measurement in vacuum through a short-circuited line.
AB - Method of voltage measurement at a vacuum load by means of homogeneous short
circuited vacuum-isolated line was considered. Prior to appearance of a measured
high-voltage pulse, a magnetic field is formed in the line due to the bias
current. Biasing provides fulfillment of magnetic electron isolation conditions
and strong pressing of an electron layer down to the cathode already at the
voltage wave front. As a result, a weak change of the "hot" line wave impedance
is achieved during a pulse. Theoretical consideration and numerical simulation of
the measuring line operation in the presence of bias current basing the
applicability of the method was carried out. The method was used to determine the
plasma-filled diode voltage at a megavolt voltage level. The absence of electron
leakages at the voltage wave propagation of the amplitude ~1 MV along the
measuring line of the length 2.3 m with the wave impedance of 136 Omega and
initial bias current of ~6 kA was realized.
PMID- 22047313
TI - Precision waveguide system for measurement of complex permittivity of liquids at
frequencies from 60 to 90 GHz.
AB - We describe a variable path length waveguide setup developed to accurately
measure the complex dielectric permittivity of liquids. This is achieved by
measuring the complex scattering parameter of the liquid in a waveguide section
with a vector network analyzer in combination with an E-band frequency converter.
The automated measurement procedure allows fast acquisition at closely spaced
intervals over the entire measurement bandwidth: 60-90 GHz. The presented
technique is an absolute method and as such is not prone to calibration errors.
The technique is suited to investigate low-loss as well as high-loss liquids in
contrast to similar setups described previously. We present measurements for a
high-loss liquid (water), an intermediate-loss sample (ethanol), and for nearly
loss-less n-octane. Due to the available phase information, the present data have
an improved accuracy in comparison with literature data.
PMID- 22047314
TI - Slippage toughness measurement of soft interface between stiff thin films and
elastomeric substrate.
AB - Traditional interfacial toughness measurements for thin films on substrate are
not appropriate to the structure composed of stiff films and soft substrate. This
paper describes a new bending test system to measure the interfacial toughness
for the soft interface between stiff films and elastomeric substrate. The
experimental setup including the loading stages is easy to operate and scanning
electron microscope is used to in situ monitor the interfacial slippage during
loading. The proposed bending test is conducted for silicon film on
poly(dimethylsiloxane) substrate. This method demonstrates the promising way to
measure the slippage toughness of soft interface involving the flexible
electronics and the bio-related fields.
PMID- 22047315
TI - Cryogenic ultra-low-noise SiGe transistor amplifier.
AB - An ultra-low-noise one-stage SiGe heterojunction bipolar transistor amplifier was
designed for cryogenic temperatures and a frequency range of 10 kHz-100 MHz. A
noise temperature T(N) ~ 1.4 K was measured at an ambient temperature of 4.2 K at
frequencies between 100 kHz and 100 MHz for a source resistance of ~50 Omega. The
voltage gain of the amplifier was 25 dB at a power consumption of 720 MUW. The
input voltage noise spectral density of the amplifier is about 35 pV/?Hz. The low
noise resistance and power consumption makes the amplifier suitable for readout
of resistively shunted DC SQUID magnetometers and amplifiers.
PMID- 22047316
TI - Pound-locking for characterization of superconducting microresonators.
AB - We present a new application and implementation of the Pound-locking technique
for the interrogation of superconducting microresonators. We discuss how by
comparing against stable frequency sources this technique can be used to
characterize properties of resonators that cannot be accessed using traditional
methods. Specifically, by analyzing the noise spectra and the Allan deviation, we
obtain valuable information about the nature of the noise in superconducting
planar resonators. This technique also greatly improves the read-out accuracy and
measurement throughput compared to conventional methods.
PMID- 22047317
TI - A travelling photothermal technique employing pyroelectric detection to measure
thermal diffusivity of films and coatings.
AB - A travelling thermal wave technique employing optical excitation and pyroelectric
detection of thermal waves propagating along a material film/coating on a
substrate is described. The method enables direct measurement of thermal
diffusivity. The technique involves measurement of the phase lag undergone by an
optically excited thermal wave as it propagates along the coating. The set up has
been automated for convenient and fast data acquisition and analysis. The
technique has been adapted to measurement of thermal diffusivity of a commercial
paint sample coated on glass and copper substrates. It is found that thermal
diffusivity of the coating is independent of the thermal conductivity of the
substrate. Dependence of thermal diffusivity on coating thickness shows
exponential increase, with value reaching a constant at a characteristic high
thickness. Measurements have been carried out on a few other samples with wide
variations in thermal diffusivity, and the results compared with available
reports or results obtained following other techniques. Analyses of the results
show that the technique allows measurement of thermal diffusivity of coatings and
films with uncertainties better than +/-2.5%.
PMID- 22047318
TI - Phase behaviour and phase separation kinetics measurement using acoustic arrays.
AB - Speed of sound and acoustic wave attenuation are sensitive to fluid phase
composition and to the presence of liquid-liquid interfaces. In this work, the
use of an acoustic array comprising 64 elements as a non-intrusive sensor for
liquid-liquid interface, phase separation kinetics measurement in bulk fluids,
and local composition measurement in porous media is illustrated. Three benchmark
examples: the phase behaviour of methanol + mixed hexanes and methanol + heptane
mixtures at 25.0 degrees C and 1 bar, and Athabasca bitumen + heptane in a
synthetic silica porous medium at 22.5 degrees C and 1 bar, illustrate the
accuracy of liquid-liquid interface and potential research and industrial
applications of the technique. Liquid-liquid interfaces can be detected
independently using both speed of sound and acoustic wave attenuation
measurements. The precision of the interface location measurement is 300 MUm. As
complete scans can be performed at a rate of 1 Hz, phase separation kinetics and
diffusion of liquids within porous media are readily tracked. The technique is
expected to find application where the fluids or porous media are opaque to
visible light and where other imaging techniques are not readily applied, or are
too costly. A current limitation is that the acoustic probes must be cooled to
less than 315 K in order for them to operate.
PMID- 22047319
TI - High-speed phosphor thermometry.
AB - Phosphor thermometry is a semi-invasive surface temperature measurement technique
utilising the luminescence properties of doped ceramic materials. Typically,
these phosphor materials are coated onto the object of interest and are excited
by a short UV laser pulse. Up to now, primarily Q-switched laser systems with
repetition rates of 10 Hz were employed for excitation. Accordingly, this
diagnostic tool was not applicable to resolve correlated temperature transients
at time scales shorter than 100 ms. This contribution reports on the first
realisation of a high-speed phosphor thermometry system employing a highly
repetitive laser in the kHz regime and a fast decaying phosphor. A suitable
material was characterised regarding its temperature lifetime characteristic and
its measurement precision. Additionally, the influence of laser power on the
phosphor coating was investigated in terms of heating effects. A demonstration of
this high-speed technique has been conducted inside the thermally highly
transient system of an optically accessible internal combustion engine.
Temperatures have been measured with a repetition rate of 6 kHz corresponding to
one sample per crank angle degree at 1000 rpm.
PMID- 22047320
TI - An accurate new method to measure the dimensionless figure of merit of
thermoelectric devices based on the complex impedance porcupine diagram.
AB - The heat diffusion related f(-1/2) slow decay in the frequency domain transfer
function of thermoelectric devices introduces a bias in figure of merit
measurement methods that do not take it into account. The bias can range from
less than 1% to more than 20% depending on the device. Harman type methods are
not immune. Neither is the simple single measurement procedure proposed here on
the basis of a complex thermal impedance analysis of the device, but in this case
the supporting theory allows evaluating and correcting for the bias with
documented accuracy. To this aim, both a theoretical approach based on a priori
knowledge of the device and an experimental one based on theory guided
measurements are possible and are described in the paper. Typical residual Type B
uncertainties after correction can be below 10% of the bias.
PMID- 22047321
TI - Non-equilibrium phonon generation and detection in microstructure devices.
AB - We demonstrate a method to excite locally a controllable, non-thermal
distribution of acoustic phonon modes ranging from 0 to ~200 GHz in a silicon
microstructure, by decay of excited quasiparticle states in an attached
superconducting tunnel junction (STJ). The phonons transiting the structure
ballistically are detected by a second STJ, allowing comparison of direct with
indirect transport pathways. This method may be applied to study how different
phonon modes contribute to the thermal conductivity of nanostructures.
PMID- 22047322
TI - Versatile computer-controlled system for characterization of gas sensing
materials.
AB - Design of a system used for characterizing gas sensing materials is described. It
is distinctive of being able to measure electrical and optical responses of a
sample simultaneously, control a number of measurement parameters, perform fast
exchange of gaseous environment, and be fully controlled automatically. These
features make the system to be versatile in determining most concerned
performance indexes of a gas sensing material (e.g., sensitivity, stability,
selectivity, response/recovery times, etc.) as functions of various combinations
of measurement conditions (e.g., gas concentrations, temperature, total pressure,
content of interferants, photo assist, relative humidity, soaking time in a fixed
gas concentration, and number of switching cycles in a dynamic test, etc.).
Rationales of the designs associated with general gas sensing mechanics are
discussed.
PMID- 22047323
TI - Implementation of a portable electronic system for providing pain relief to
patellofemoral pain syndrome patients.
AB - In this study, a portable electromyogram (EMG) system and a stimulator are
developed for patellofemoral pain syndrome patients, with the objective of
reducing the pain experienced by these patients; the patellar pain is caused by
an imbalance between the vastus medialis obliquus (VMO) and the vastus lateralis
(VL). The EMG measurement circuit and the electrical stimulation device proposed
in this study are specifically designed for the VMO and the VL; they are capable
of real-time waveform recording, possess analyzing functions, and can upload
their measurement data to a computer for storage and analysis. The system can
calculate and record the time difference between the EMGs of the VMO and the VL,
as well as the signal strengths of both the EMGs. As soon as the system detects
the generation of the EMG of the VL, it quickly calculates and processes the
event and stimulates the VMO as feedback through electrical stimulation units, in
order to induce its contraction. The system can adjust the signal strength, time
length, and the sequence of the electrical stimulation, both manually and
automatically. The output waveform of the electrical stimulation circuit is a
dual-phase asymmetrical pulse waveform. The primary function of the electrical
simulation circuit is to ensure that the muscles contract effectively. The
performance of the device can be seen that the width of each pulse is 20-1000
MUs, the frequency of each pulse is 10-100 Hz, and current strength is 10-60 mA.
PMID- 22047324
TI - A dynamic gravimetric standard for trace water.
AB - A system for generating traceable reference standards of water vapor at trace
levels between 5 and 2000 nmol/mol has been developed. It can provide different
amount fractions of trace water vapor by using continuous accurate measurements
of mass loss from a permeation device coupled with a dilution system based on an
array of critical flow orifices. An estimated relative expanded uncertainty of +/
2% has been achieved for most amount fractions generated. The system has been
used in an international comparison and demonstrates excellent comparability with
National Metrology Institutes maintaining standards of water vapor in this range
using other methods.
PMID- 22047325
TI - Large angle and high linearity two-dimensional laser scanner based on voice coil
actuators.
AB - A large angle and high linearity two-dimensional laser scanner with an in-house
ingenious deflection angle detecting system is developed based on voice coil
actuators direct driving mechanism. The specially designed voice coil actuators
make the steering mirror moving at a sufficiently large angle. Frequency sweep
method based on virtual instruments is employed to achieve the natural frequency
of the laser scanner. The response shows that the performance of the laser
scanner is limited by the mechanical resonances. The closed-loop controller based
on mathematical model is used to reduce the oscillation of the laser scanner at
resonance frequency. To design a qualified controller, the model of the laser
scanner is set up. The transfer function of the model is identified with MATLAB
according to the tested data. After introducing of the controller, the
nonlinearity decreases from 13.75% to 2.67% at 50 Hz. The laser scanner also has
other advantages such as large deflection mirror, small mechanical structure, and
high scanning speed.
PMID- 22047326
TI - Dust trajectory sensor: accuracy and data analysis.
AB - The Dust Trajectory Sensor (DTS) instrument is developed for the measurement of
the velocity vector of cosmic dust particles. The trajectory information is
imperative in determining the particles' origin and distinguishing dust particles
from different sources. The velocity vector also reveals information on the
history of interaction between the charged dust particle and the magnetospheric
or interplanetary space environment. The DTS operational principle is based on
measuring the induced charge from the dust on an array of wire electrodes. In
recent work, the DTS geometry has been optimized [S. Auer, E. Grun, S. Kempf, R.
Srama, A. Srowig, Z. Sternovsky, and V Tschernjawski, Rev. Sci. Instrum. 79,
084501 (2008)] and a method of triggering was developed [S. Auer, G. Lawrence, E.
Grun, H. Henkel, S. Kempf, R. Srama, and Z. Sternovsky, Nucl. Instrum. Methods
Phys. Res. A 622, 74 (2010)]. This article presents the method of analyzing the
DTS data and results from a parametric study on the accuracy of the measurements.
A laboratory version of the DTS has been constructed and tested with particles in
the velocity range of 2-5 km/s using the Heidelberg dust accelerator facility.
Both the numerical study and the analyzed experimental data show that the
accuracy of the DTS instrument is better than about 1% in velocity and 1 degrees
in direction.
PMID- 22047327
TI - Photoelectron-photofragment coincidence spectroscopy in a cryogenically cooled
linear electrostatic ion beam trap.
AB - A cryogenically cooled linear electrostatic ion beam trap for use in
photoelectron-photofragment coincidence (PPC) spectroscopy is described. Using
this instrument, anions created in cold, low-duty-cycle sources can be stored for
many seconds in a ~20 K environment to cool radiatively, removing energetic
uncertainties due to vibrationally excited precursor anions. This apparatus
maintains a well-collimated beam necessary for high-resolution fragment imaging
and the high experimental duty cycle needed for coincidence experiments. Ion
oscillation is bunched and phase-locked to a modelocked laser, ensuring temporal
overlap between ion bunches and laser pulses and that ions are intersected by the
laser only when travelling in one direction. An electron detector is housed in
the field-free center of the trap, allowing PPC experiments to be carried out on
ions while they are stored and permitting efficient detection of 3-dimensional
electron and neutral recoil trajectories. The effects of trapping parameters on
the center-of-mass trajectories in the laser-ion interaction region are explored
to optimize neutral particle resolution, and the impact of bunching on ion
oscillation is established. Finally, an initial demonstration of radiative
cooling is presented.
PMID- 22047328
TI - Development of the heat treatment system for the 40 T hybrid magnet
superconducting outsert.
AB - The heat treatment of Nb(3)Sn coil with the glass fabric insulation is one of the
key and critical processes for the outsert solenoids of the 40 T hybrid magnet,
which could be wound with cable-in-conduit conductors using the insulation-wind
and-react technique. The manufacturing of the large vertical type vacuum/Ar
atmosphere-protection heat treatment system has been completed and recently
installed in the High Magnetic Filed Laboratory, Chinese Academy of Sciences. The
heat treatment system composed mainly the furnace, the purging gas supply system,
the control system, the gas impurities monitoring system, and so on. At present,
the regulation and testing of the heat treatment system has been successfully
finished, and all of technical parameters meet or exceed specifications.
PMID- 22047329
TI - A design of backing seat and gasket assembly in diamond anvil cell for accurate
single crystal x-ray diffraction to 5 GPa.
AB - We designed a new cell assembly of diamond anvil cells for single crystal x-ray
diffraction under pressure and demonstrate the application of the cell to the
crystallographic studies for ice VI and ethanol high-pressure (HP) phase at
0.95(5) GPa and 1.95(2) GPa, respectively. The features of the assembly are: (1)
the platy anvil and unique-shaped backing seat (called as "Wing seat") allowing
the extremely wide opening angle up to +/-65 degrees , (2) the PFA-bulk metallic
glass composite gasket allowing the easy attenuation correction and less
background. Thanks to the designed assembly, the R(int) values after attenuation
corrections are fairly good (0.0125 and 0.0460 for ice VI and ethanol HP phase,
respectively), and the errors of the refined parameters are satisfactory small
even for hydrogen positions, those are comparable to the results which obtained
at ambient conditions. The result for ice VI is in excellent agreement with the
previous study, and that for ethanol HP phase has remarkable contributions to the
revision to its structure; the H12 site, which makes gauche molecules with O1,
C2, and C3 sites, may not exist so that only trans conformers are present at
least at 1.95(2) GPa. The accurate intensities using the cell assembly allow us
to extract the electron density for ethanol HP phase by the maximum entropy
method.
PMID- 22047330
TI - Compact x-ray microradiograph for in situ imaging of solidification processes:
bringing in situ x-ray micro-imaging from the synchrotron to the laboratory.
AB - A laboratory based high resolution x-ray radiograph was developed for the
investigation of solidification dynamics in alloys. It is based on a low-power
microfocus x-ray tube and is potentially appropriate for x-ray diagnostics in
space. The x-ray microscope offers a high spatial resolution down to
approximately 5 MUm. Dynamic processes can be resolved with a frequency of up to
6 Hz. In reference experiments, the setup was optimized to yield a high contrast
for AlCu-alloys. With samples of about 150 MUm thickness, high quality image
sequences of the solidification process were obtained with high resolution in
time and space.
PMID- 22047331
TI - Cryogenic implementation of charging diamond anvil cells with H2 and D2.
AB - A cryogenic loading system for introducing H(2) and D(2) into the diamond anvil
cell has been designed and constructed. The integration of pressure loading
mechanism, ruby fluorescence spectrometer, and microscope camera allows for in
situ tuning and calibrating the pressure. The performance of the system has been
demonstrated by successful synthesis of hydride and deuteride of transition metal
and rare earth metal. Our cryogenic methodology features facile start-over of
loading and in situ electrical resistance measurement of as-synthesized sample.
PMID- 22047332
TI - Fast template tracking in video sequences.
AB - Tracking of poorly defined, rotating and/or distorted objects in a video sequence
poses significant problems especially in medical diagnostics including ultrasound
(sonographic) video used for examination and diagnosis of internal movement of
tissue or muscle and nerve action. Cross-correlation techniques have been
successful in retrieving dynamic information directly from ultrasound video data.
We outline a fast implementation of tracking based on normalized cross
correlation using an adaptive template and present results from our application,
developed in MATLABTM, which successfully tracks arbitrarily selected objects in
deformed or severely compromised images. Common ultrasound image evaluation is
qualitative but there is need to retrieve quantitative dynamic information such
as the trajectory or velocity of selected areas. Our approach uses normalized two
dimensional cross-correlation to find the position of an initially selected
template enclosing the feature of interest and map its trajectory frame-by-frame
to produce displacement and velocity plots. We illustrate operation of the
application using routine ultrasound data and demonstrate its performance using
test video of objects rotating full circle and rolling down a ramp. We analyse
errors associated with sampling to compare performance of our implementation with
a more rigorous but tedious and computationally expensive correlation of a
resampled, rotated, and shifted template.
PMID- 22047333
TI - Analysis of the particle stability in a new designed ultrasonic levitation
device.
AB - The use of acoustic levitation in the fields of analytical chemistry and in the
containerless processing of materials requires a good stability of the levitated
particle. However, spontaneous oscillations and rotation of the levitated
particle have been reported in literature, which can reduce the applicability of
the acoustic levitation technique. Aiming to reduce the particle oscillations,
this paper presents the analysis of the particle stability in a new acoustic
levitator device. The new acoustic levitator consists of a piezoelectric
transducer with a concave radiating surface and a concave reflector. The analysis
is conducted by determining numerically the axial and lateral forces that act on
the levitated object and by measuring the oscillations of a sphere particle by a
laser Doppler vibrometer. It is shown that the new levitator design allows to
increase the lateral forces and reduce significantly the lateral oscillations of
the levitated object.
PMID- 22047334
TI - Expanded beam deflection method for simultaneous measurement of displacement and
vibrations of multiple microcantilevers.
AB - Here we present an extension of optical beam deflection (OBD) method for
measuring displacement and vibrations of an array of microcantilevers. Instead of
focusing on the cantilever, the optical beam is either focused above or below the
cantilever array, or focused only in the axis parallel to the cantilevers length,
allowing a wide optical line to span multiple cantilevers in the array. Each
cantilever reflects a part of the incident beam, which is then directed onto a
photodiode array detector in a manner allowing distinguishing between individual
beams. Each part of reflected beam behaves like a single beam of roughly the same
divergence angle in the bending sensing axis as the incident beam. Since
sensitivity of the OBD method depends on the divergence angle of deflected beam,
high sensitivity is preserved in proposed expanded beam deflection (EBD) method.
At the detector, each spot's position is measured at the same time, without time
multiplexing of light sources. This provides real simultaneous readout of entire
array, unavailable in most of competitive methods, and thus increases time
resolution of the measurement. Expanded beam can also span another line of
cantilevers allowing monitoring of specially designed two-dimensional arrays. In
this paper, we present first results of application of EBD method to cantilever
sensors. We show how thermal noise resolution can be easily achieved and combined
with thermal noise based resonance frequency measurement.
PMID- 22047335
TI - Optimization of a vacuum chamber for vibration measurements.
AB - A 200 degrees C high vacuum chamber has been built to improve vibration
measurement sensitivity. The optimized design addresses two significant issues:
(i) vibration measurements under high vacuum conditions and (ii) use of design
optimization tools to reduce operating costs. A test rig consisting of a
cylindrical vessel with one access port has been constructed with a welded
bellows assembly used to seal the vessel and enable vibration measurements in
high vacuum that are comparable with measurements in air. The welded-bellows
assembly provides a force transmissibility of 0.1 or better at 15 Hz excitation
under high vacuum conditions. Numerical results based on design optimization of a
larger diameter chamber are presented. The general constraints on the new design
include material yield stress, chamber first natural frequency, vibration
isolation performance, and forced convection heat transfer capabilities over the
exterior of the vessel access ports. Operating costs of the new chamber are
reduced by 50% compared to a preexisting chamber of similar size and function.
PMID- 22047336
TI - A magnetically driven piston pump for ultra-clean applications.
AB - A magnetically driven piston pump for xenon gas recirculation is presented. The
pump is designed to satisfy extreme purity and containment requirements, as is
appropriate for the recirculation of isotopically enriched xenon through the
purification system and large liquid xenon time projection chamber of EXO-200.
The pump, using sprung polymer gaskets, is capable of pumping more than 16
standard liters per minute of xenon gas with 750 Torr differential pressure.
PMID- 22047337
TI - Elastic incoherent neutron scattering operating by varying instrumental energy
resolution: principle, simulations, and experiments of the resolution elastic
neutron scattering (RENS).
AB - The main aim of this paper is to present the scientific case of the resolution
elastic neutron scattering (RENS) method that is based on the collection of
elastic neutron scattering intensity as a function of the instrumental energy
resolution and that is able to extract information on the system dynamical
properties from an elastic signal. In this framework, it is shown that in the
measured elastic scattering law, as a function of the instrumental energy
resolution, an inflection point occurs when the instrumental energy resolution
intersects the system relaxation time, and in an equivalent way, a transition in
the temperature behavior of the measured elastic scattering law occurs when the
characteristic system relaxation time crosses the instrumental energy resolution
time. With regard to the latter, an operative protocol to determine the system
characteristic time by different elastic incoherent neutron scattering (EINS)
thermal scans at different instrumental energy resolutions is also proposed. The
proposed method, hence, is not primarily addressed to collect the measured
elastic scattering intensity with a great accuracy, but rather relies on
determining an inflection point in the measured elastic scattering law versus
instrumental energy resolution. The RENS method is tested both numerically and
experimentally. As far as numerical simulations are concerned, a simple model
system for which the temperature behavior of the relaxation time follows an
Arrhenius law, while its scattering law follows a Gaussian behavior, is
considered. It is shown that the system relaxation time used as an input for the
simulations coincides with the one obtained by the RENS approach. Regarding the
experimental findings, due to the fact that a neutron scattering spectrometer
working following the RENS method has not been constructed yet, different EINS
experiments with different instrumental energy resolutions were carried out on a
complex model system, i.e., dry and D(2)O hydrated lysozyme, in an extended
temperature range. The resulting temperature behavior of the system relaxation
time, obtained with RENS method, agrees very well with the one obtained in
literature, for the same system, following the quasi-elastic neutron scattering
(QENS) approach. The proposed scientific case puts into evidence the challenges
of an RENS spectrometer working by varying the instrumental energy resolution; in
particular, in comparison with QENS, the proposed RENS method requires a smaller
amount of sample, which is an important point in dealing with biological and
exotic systems; it is not affected by the use of model functions for fitting
spectra as in QENS, but furnishes a direct access to relevant information.
PMID- 22047338
TI - A generalized analytical compliance model for transversely symmetric three
segment flexure hinges.
AB - This paper presents a generalized compliance model for a three-segment notch
flexure hinge with transverse symmetry. This flexure hinge configuration is most
frequently employed in planar-motion, small-displacement compliant mechanisms.
The axial and bending compliances are derived for this flexure hinge based on the
compliances of two flexure components. The derivation is generalized such that it
can be applied to various segment geometries. Using this open-ended model, a
three-segment right elliptical corner-filleted flexure hinge design was analyzed.
This geometric configuration introduces additional geometric parameters, which
can be used to optimize the compliance of the flexure hinge without modifying its
gross dimensions. The results of the analysis were validated in part by modifying
the geometric parameters of the center segment and elliptical corner fillets to
form limiting cases corresponding to several previously investigated
configurations, namely right elliptical, three-segment right circular corner
filleted, and right circular geometries. Finite element analysis simulation and
experimental testing were used to further validate the three-segment right
elliptical corner-filleted analytical model. Additional simulations based on the
analytical model were performed to highlight the influence of geometric
parameters on compliances and to investigate shear effects for short flexure
hinges.
PMID- 22047339
TI - Note: Simultaneous electrical and optical detection of expanding dense partially
ionized vapour clouds.
AB - The scheme and construction of an electro-optical probe able to collect charge
and detect optical emission from expanding dense partially ionized vapour clouds
are reported. The instrument can be applied to phenomena such as dust impact
ionization and solid target laser ablation. First, results of measurements of
expanding plasma cloud formed upon ablating W target are presented. Use of the
instrument in different experimental facilities, including tokamak, is discussed.
PMID- 22047340
TI - Note: A novel method for in situ loading of gases via x-ray induced chemistry.
AB - We have developed and demonstrated a novel method to load oxygen in a sealed
diamond anvil cell via the x-ray induced decomposition of potassium chlorate. By
irradiating a pressurized sample of an oxidizer (KClO(3)) with either
monochromatic or white beam x-rays from the Advanced Photon Source at ambient
temperature and variable pressure, we succeeded in creating a localized region of
molecular oxygen surrounded by unreacted sample which was confirmed via Raman
spectroscopy. We anticipate that this technique will be useful in loading even
more challenging, difficult-to-load gases such as hydrogen and also to load
multiple gases.
PMID- 22047341
TI - Note: Compact high voltage pulse transformer made using a capacitor bank
assembled in the shape of primary.
AB - The experimental results of an air-core pulse transformer are presented, which is
very compact (<10 Kg in weight) and is primed by a capacitor bank that is
fabricated in such a way that the capacitor bank with its switch takes the shape
of single-turn rectangular shaped primary of the transformer. A high voltage
capacitor assembly (pulse-forming-line capacitor, PFL) of 5.1 nF is connected
with the secondary of transformer. The transformer output voltage is 160 kV in
its second peak appearing in less than 2 MUS from the beginning of the capacitor
discharge. The primary capacitor bank can be charged up to a maximum of 18 kV,
with the voltage delivery of 360 kV in similar capacitive loads.
PMID- 22047342
TI - Note: Recent achievements at the 60-MeV linac for sub-picosecond terahertz
radiation at the Pohang Accelerator Laboratory.
AB - A femtosecond (fs) terahertz (THz) linac has been constructed to generate fs-THz
radiation by using ultrashort electron beam at the Pohang Accelerator Laboratory.
To generate an ultrashort electron beam with 60-MeV energy, a chicane bunch
compressor has been adopted. Simulation studies have been conducted to design the
linac. In this note, recent achievements at 60-MeV linac are presented.
PMID- 22047343
TI - Note: Mechanical and electrical characterization of nanowires in scanning
electron microscope.
AB - This note presents two experimental techniques for mechanical and electrical
characterization of individual nanowires inside a scanning electron microscope
(SEM). Tensile testing is realized by transferring a nanowire to a
microelectromechanical systems device that stretches the nanowire and measures
the elongations and tensile forces. The device consists of an electrostatic
actuator and two capacitive sensors, capable of acquiring all measurement data
(force and displacement) electronically without relying on electron microscopy
imaging. For electrical characterization, four-point probe measurement of
individual nanowires is performed automatically by controlling four
nanomanipulators with SEM visual feedback. A feedforward controller is
incorporated into the control system to improve the response time. This work
represents advances in nanomaterial testing and automated nanomanipulation.
PMID- 22047344
TI - Note: Continuing improvements on the novel flat-response x-ray detector.
AB - This note describes multi-updates of the novel flat-response x-ray detector in
fabrication technology, experimental application, and data uncertainty
evaluation. Unlike the previous design, the compound filter is combined into one
piece through an improved fabrication process that greatly enhanced its self
supporting capability. A method of pinhole-array imaging is introduced into the
experimental application process to stop any debris from the hohlraum and to
uniformly reduce the radiation flux. The experimental results show that this
method works well. Furthermore, a method of uncertainty evaluation of the
radiation flux measurement by the novel flat-response x-ray detector has been
developed. The influence of the radiation spectrum to the flux measurement is
analyzed. The evaluation shows that the relative uncertainty of the radiation
flux is about 10% in higher radiation temperature condition (Tr > 150 eV) and 16%
in lower radiation temperature condition (Tr < 100 eV).
PMID- 22047346
TI - Point/Counterpoint: QA procedures in radiation therapy are outdated and
negatively impact the reduction of errors.
PMID- 22047347
TI - Interfraction patient motion and implant displacement in prostate high dose rate
brachytherapy.
AB - PURPOSE: To quantify movement of prostate cancer patients undergoing treatment,
using an in-house developed motion sensor in order to determine a relationship
between patient movement and high dose rate (HDR) brachytherapy implant
displacement. METHODS: An electronic motion sensor was developed based on a three
axis accelerometer. HDR brachytherapy treatment for prostate is delivered at this
institution in two fractions 24 h apart and 22 patients were monitored for
movement over the interval between fractions. The motion sensors functioned as
inclinometers, monitoring inclination of both thighs, and the inclination and
roll of the abdomen. The implanted HDR brachytherapy catheter set was assessed
for displacement relative to fiducial markers in the prostate. Angle measurements
and angle differences over a 2 s time base were binned, and the standard
deviations of the resulting frequency distributions used as a metric for patient
motion in each monitored axis. These parameters were correlated to measured
catheter displacement using regression modeling. RESULTS: The mean implant
displacement was 12.6 mm in the caudal direction. A mean of 19.95 h data was
recorded for the patient cohort. Patients generally moved through a limited range
of angles with a mean of the exception of two patients who spent in excess of 2 h
lying on their side. When tested for a relationship between movement in any of
the four monitored axes and the implant displacement, none was significant.
CONCLUSIONS: It is not likely that patient movement influences HDR prostate
implant displacement. There may be benefits to patient comfort if nursing
protocols were relaxed to allow patients greater freedom to move while the
implant is in situ.
PMID- 22047348
TI - On the role of the optimization algorithm of RapidArc((r)) volumetric modulated
arc therapy on plan quality and efficiency.
AB - PURPOSE: The RapidArc volumetric modulated arc therapy (VMAT) planning process is
based on a core engine, the so-called progressive resolution optimizer (PRO).
This is the optimization algorithm used to determine the combination of field
shapes, segment weights (with dose rate and gantry speed variations), which best
approximate the desired dose distribution in the inverse planning problem. A
study was performed to assess the behavior of two versions of PRO. These two
versions mostly differ in the way continuous variables describing the modulated
arc are sampled into discrete control points, in the planning efficiency and in
the presence of some new features. The analysis aimed to assess (i) plan quality,
(ii) technical delivery aspects, (iii) agreement between delivery and
calculations, and (iv) planning efficiency of the two versions. METHODS: RapidArc
plans were generated for four groups of patients (five patients each): anal
canal, advanced lung, head and neck, and multiple brain metastases and were
designed to test different levels of planning complexity and anatomical features.
Plans from optimization with PRO2 (first generation of RapidArc optimizer) were
compared against PRO3 (second generation of the algorithm). Additional plans were
optimized with PRO3 using new features: the jaw tracking, the intermediate dose
and the air cavity correction options. RESULTS: Results showed that (i) plan
quality was generally improved with PRO3 and, although not for all parameters,
some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3
optimization leads to simpler patterns of the dynamic parameters particularly for
dose rate. (iii) No differences were observed between the two algorithms in terms
of pretreatment quality assurance measurements and (iv) PRO3 optimization was
generally faster, with a time reduction of a factor approximately 3.5 with
respect to PRO2. CONCLUSIONS: These results indicate that PRO3 is either
clinically beneficial or neutral in terms of dosimetric quality while it showed
significant advantages in speed and technical aspects.
PMID- 22047349
TI - Evaluation of brachytherapy lung implant dose distributions from photon-emitting
sources due to tissue heterogeneities.
AB - PURPOSE: Photon-emitting brachytherapy sources are used for permanent
implantation to treat lung cancer. However, the current brachytherapy dose
calculation formalism assumes a homogeneous water medium without considering the
influence of radiation scatter or tissue heterogeneities. The purpose of this
study was to determine the dosimetric effects of tissue heterogeneities for
permanent lung brachytherapy. METHODS: The MCNP5 v1.40 radiation transport code
was used for Monte Carlo (MC) simulations. Point sources with energies of 0.02,
0.03, 0.05, 0.1, 0.2, and 0.4 MeV were simulated to cover the range of pertinent
brachytherapy energies and to glean dosimetric trends independent of specific
radionuclide emissions. Source positions from postimplant CT scans of five
patient implants were used for source coordinates, with dose normalized to 200 Gy
at the center of each implant. With the presence of fibrosis (around the
implant), cortical bone, lung, and healthy tissues, dose distributions and
(PTV)DVH were calculated using the MCNP *FMESH4 tally and the NIST mass-energy
absorption coefficients. This process was repeated upon replacing all tissues
with water. For all photon energies, 10(9) histories were simulated to achieve
statistical errors (k = 1) typically of 1%. RESULTS: The mean PTV doses
calculated using tissue heterogeneities for all five patients changed (compared
to dose to water) by only a few percent over the examined photon energy range, as
did PTV dose at the implant center. The (PTV)V(100) values were 81.2%, 90.0% (as
normalized), 94.3%, 93.9%, 92.7%, and 92.2% for 0.02, 0.03, 0.05, 0.1, 0.2, and
0.4 MeV source photons, respectively. Relative to water, the maximum bone doses
were higher by factors of 3.7, 5.1, 5.2, 2.4, 1.2, and 1.0 The maximum lung doses
were about 0.98, 0.94, 0.91, 0.94, 0.97, and 0.99. Relative to water, the maximum
healthy tissue doses at the mediastinal position were higher by factors of 9.8,
2.2, 1.3, 1.1, 1.1, and 1.1. However, the maximum doses to these healthy tissues
were only 3.1, 7.2, 11.3, 10.9, 9.0, and 8.1 Gy while maximum bone doses were 66,
177, 236, 106, 49, and 39 Gy, respectively. Similarly, maximum lung doses were
55, 66, 73, 74, 73, and 73 Gy, respectively. CONCLUSIONS: The current
brachytherapy dose calculation formalism overestimates PTV dose and significantly
underestimates doses to bone and healthy tissue. Further investigation using
specific brachytherapy source models and patient-based CT datasets as MC input
may indicate whether the observed trends can be generalized for low-energy lung
brachytherapy dosimetry.
PMID- 22047350
TI - Evaluation of volumetric modulated arc therapy for cranial radiosurgery using
multiple noncoplanar arcs.
AB - PURPOSE: To evaluate a commercial volumetric modulated arc therapy (VMAT), using
multiple noncoplanar arcs, for linac-based cranial radiosurgery, as well as
evaluate the combined accuracy of the VMAT dose calculations and delivery.
METHODS: Twelve patients with cranial lesions of variable size (0.1-29 cc) and
two multiple metastases patients were planned (Eclipse RapidArc AAA algorithm,
v8.6.15) using VMAT (1-6 noncoplanar arcs), dynamic conformal arc (DCA, ~4 arcs),
and IMRT (nine static fields). All plans were evaluated according to a conformity
index (CI), healthy brain tissue doses and volumes, and the dose to organs at
risk. A 2D dose distribution was measured (Varian Novalis Tx, HD120 MLC, 1000
MU/min, 6 MV beam) for the ~4 arc VMAT treatment plans using calibrated film
dosimetry. RESULTS: The CI (0-1 best) average for all plans was best for ~4
noncoplanar arc VMAT at 0.86 compared with ~0.78 for IMRT and a single arc VMAT
and 0.68 for DCA. The volumes of healthy brain receiving 50% of the prescribed
target coverage dose or more (V(50%)) were lowest for the four arc VMAT [RA(4)]
and DCA plans. The average ratio of the V(50%) for the other plans to the RA(4)
V(50%) were 1.9 for a single noncoplanar arc VMAT [RA(1nc)], 1.4 for single full
coplanar arc VMAT [RA(1f)] and 1.3 for IMRT. The V(50%) improved significantly
for single isocenter multiple metastases plan when two noncoplanar VMAT arcs were
added to a full single coplanar one. The maximum dose to 5 cc of the outer 1 cm
rim of healthy brain which one may want to keep below nonconsequential doses of
300-400 cGy, was 2-3 times greater for IMRT, RA(1nc) and RA(1f) plans compared
with the multiple noncoplanar arc DCA and RA(4) techniques. Organs at risk near
(0-4 mm) to targets were best spared by (i) single noncoplanar arcs when the
targets are lateral to the organ at risk and (ii) by skewed nonvertical planes of
IMRT fields when the targets are not lateral to the organ at risk. The highest
dose gradient observed between an organ at risk and a target at the edge of a
VMAT arc plane or plane of IMRT fields was 17%/mm. The average absolute percent
difference between the measured and calculated central axis dose for all the VMAT
plans was 3.6 +/- 2.2%. The measured perpendicular profile widths and shifts were
on average within 0.5 mm of planned values. The average total MUs for VMAT plans
was double the DCA average and similar to the IMRT average. CONCLUSIONS: For the
aforementioned planning and delivery system and cranial lesions greater than 7 mm
in diameter, multiple noncoplanar arc VMAT consistently provides accurate and
high quality cranial radiosurgery dose distributions with low doses to healthy
brain tissue and high dose conformity to the target. These qualities may make
multiple noncoplanar arc VMAT suitable for a greater range of prescription doses
or larger and more irregular lesions. For smaller and/or rounder lesions there
are other clinically acceptable treatment techniques that may involve fewer couch
angles or arcs and reduce treatment times.
PMID- 22047351
TI - A handheld fluorescence molecular tomography system for intraoperative optical
imaging of tumor margins.
AB - PURPOSE: Accurate identification of tumor margins presents a major challenge in
the surgical treatment of human cancers. Inability of complete removal of tumor
lesions after surgery causes local recurrence and increases the incidence of
developing tumor metastasis. It is clear that novel approaches that allow
defining tumor margins intraoperatively for removal of small tumor lesions in the
surgical cavity is critical for improving prognosis of cancer patients. To
facilitate image-guided surgery using targeted optical imaging probes, we have
developed a reflection-mode fluorescence molecular tomography (FMT) system with a
handheld probe that is able to provide three-dimensional tumor margin
information. METHODS: The imaging method and system were validated using both
simulated and phantom experiments. We further examined the accuracy of the
handheld FMT system in an orthotopic mouse mammary tumor model following systemic
delivery of near-infrared (NIR) dye-labeled and urokinase plasminogen activator
receptor targeted magnet iron oxide nanoparticles. RESULTS: Our results show that
when the targets are located within 5 mm beneath the surface of the media,
fluorescent images can be reliably detected and reconstructed with an average
positional error of 0.5 mm laterally and 1.5 mm axially. For in vivo imaging in
the mouse tumor model, the location and size of the tumor detected by FMT
correlated well with that measured by the magnetic resonance imaging (MRI).
CONCLUSIONS: Our system can three-dimensionally image targets located at a depth
of up to 7 mm. The in vivo results suggest that in combination with targeted
optical imaging probes, this handheld FMT system can be potentially used as an
intraoperative tool for the detection of tumor margins and for image-guided
surgery.
PMID- 22047352
TI - Automated temporal tracking and segmentation of lymphoma on serial CT
examinations.
AB - PURPOSE: It is challenging to reproducibly measure and compare cancer lesions on
numerous follow-up studies; the process is time-consuming and error-prone. In
this paper, we show a method to automatically and reproducibly identify and
segment abnormal lymph nodes in serial computed tomography (CT) exams. METHODS:
Our method leverages initial identification of enlarged (abnormal) lymph nodes in
the baseline scan. We then identify an approximate region for the node in the
follow-up scans using nonrigid image registration. The baseline scan is also used
to locate regions of normal, non-nodal tissue surrounding the lymph node and to
map them onto the follow-up scans, in order to reduce the search space to locate
the lymph node on the follow-up scans. Adaptive region-growing and clustering
algorithms are then used to obtain the final contours for segmentation. We
applied our method to 24 distinct enlarged lymph nodes at multiple time points
from 14 patients. The scan at the earlier time point was used as the baseline
scan to be used in evaluating the follow-up scan, resulting in 70 total test
cases (e.g., a series of scans obtained at 4 time points results in 3 test
cases). For each of the 70 cases, a "reference standard" was obtained by manual
segmentation by a radiologist. Assessment according to response evaluation
criteria in solid tumors (RECIST) using our method agreed with RECIST assessments
made using the reference standard segmentations in all test cases, and by
calculating node overlap ratio and Hausdorff distance between the computer and
radiologist-generated contours. RESULTS: Compared to the reference standard, our
method made the correct RECIST assessment for all 70 cases. The average overlap
ratio was 80.7 +/- 9.7% s.d., and the average Hausdorff distance was 3.2 +/- 1.8
mm s.d. The concordance correlation between automated and manual segmentations
was 0.978 (95% confidence interval 0.962, 0.984). The 100% agreement in our
sample between our method and the standard with regard to RECIST classification
suggests that the true disagreement rate is no more than 6%. CONCLUSIONS: Our
automated lymph node segmentation method achieves excellent overall segmentation
performance and provides equivalent RECIST assessment. It potentially will be
useful to streamline and improve cancer lesion measurement and tracking and to
improve assessment of cancer treatment response.
PMID- 22047353
TI - A PENELOPE-based system for the automated Monte Carlo simulation of clinacs and
voxelized geometries-application to far-from-axis fields.
AB - PURPOSE: Two new codes, PENEASY and PENEASYLINAC, which automate the Monte Carlo
simulation of Varian Clinacs of the 600, 1800, 2100, and 2300 series, together
with their electron applicators and multileaf collimators, are introduced. The
challenging case of a relatively small and far-from-axis field has been studied
with these tools. METHODS: PENEASY is a modular, general-purpose main program for
the PENELOPE Monte Carlo system that includes various source models, tallies and
variance-reduction techniques (VRT). The code includes a new geometry model that
allows the superposition of voxels and objects limited by quadric surfaces. A
variant of the VRT known as particle splitting, called fan splitting, is also
introduced. PENEASYLINAC, in turn, automatically generates detailed geometry and
configuration files to simulate linacs with PENEASY. These tools are applied to
the generation of phase-space files, and of the corresponding absorbed dose
distributions in water, for two 6 MV photon beams from a Varian Clinac 2100 C/D:
a 40 * 40 cm(2) centered field; and a 3 * 5 cm(2) field centered at (4.5, -11.5)
cm from the beam central axis. This latter configuration implies the largest
possible over-traveling values of two of the jaws. Simulation results for the
depth dose and lateral profiles at various depths are compared, by using the
gamma index, with experimental values obtained with a PTW 31002 ionization
chamber. The contribution of several VRTs to the computing speed of the more
demanding off-axis case is analyzed. RESULTS: For the 40 * 40 cm(2) field, the
percentages gamma(1) and gamma(1.2) of voxels with gamma indices (using 0.2 cm
and 2% criteria) larger than unity and larger than 1.2 are 0.2% and 0%,
respectively. For the 3 * 5 cm(2) field, gamma(1) = 0%. These figures indicate an
excellent agreement between simulation and experiment. The dose distribution for
the off-axis case with voxels of 2.5 * 2.5 * 2.5 mm(3) and an average standard
statistical uncertainty of 2% (1sigma) is computed in 3.1 h on a single core of a
2.8 GHz Intel Core 2 Duo processor. This result is obtained with the optimal
combination of the tested VRTs. In particular, fan splitting for the off-axis
case accelerates execution by a factor of 240 with respect to standard particle
splitting. CONCLUSIONS: PENEASY and PENEASYLINAC can simulate the considered
Varian Clinacs both in an accurate and efficient manner. Fan splitting is crucial
to achieve simulation results for the off-axis field in an affordable amount of
CPU time. Work to include Elekta linacs and to develop a graphical interface that
will facilitate user input is underway.
PMID- 22047354
TI - Three-dimensional anisotropic adaptive filtering of projection data for noise
reduction in cone beam CT.
AB - PURPOSE: The combination of quickly rotating C-arm gantry with digital flat panel
has enabled the acquisition of three-dimensional data (3D) in the interventional
suite. However, image quality is still somewhat limited since the hardware has
not been optimized for CT imaging. Adaptive anisotropic filtering has the ability
to improve image quality by reducing the noise level and therewith the radiation
dose without introducing noticeable blurring. By applying the filtering prior to
3D reconstruction, noise-induced streak artifacts are reduced as compared to
processing in the image domain. METHODS: 3D anisotropic adaptive filtering was
used to process an ensemble of 2D x-ray views acquired along a circular
trajectory around an object. After arranging the input data into a 3D space (2D
projections + angle), the orientation of structures was estimated using a set of
differently oriented filters. The resulting tensor representation of local
orientation was utilized to control the anisotropic filtering. Low-pass filtering
is applied only along structures to maintain high spatial frequency components
perpendicular to these. The evaluation of the proposed algorithm includes
numerical simulations, phantom experiments, and in-vivo data which were acquired
using an AXIOM Artis dTA C-arm system (Siemens AG, Healthcare Sector, Forchheim,
Germany). Spatial resolution and noise levels were compared with and without
adaptive filtering. A human observer study was carried out to evaluate low
contrast detectability. RESULTS: The adaptive anisotropic filtering algorithm was
found to significantly improve low-contrast detectability by reducing the noise
level by half (reduction of the standard deviation in certain areas from 74 to 30
HU). Virtually no degradation of high contrast spatial resolution was observed in
the modulation transfer function (MTF) analysis. Although the algorithm is
computationally intensive, hardware acceleration using Nvidia's CUDA Interface
provided an 8.9-fold speed-up of the processing (from 1336 to 150 s).
CONCLUSIONS: Adaptive anisotropic filtering has the potential to substantially
improve image quality and/or reduce the radiation dose required for obtaining 3D
image data using cone beam CT.
PMID- 22047355
TI - Development of a prototype gantry system for preclinical x-ray phase-contrast
computed tomography.
AB - PURPOSE: To explore the potential of grating-based x-ray phase-contrast imaging
for clinical applications, a first compact gantry system was developed. It is
designed such that it can be implemented into an in-vivo small-animal phase
contrast computed tomography (PC-CT) scanner. The purpose of the present study is
to assess the accuracy and quantitativeness of the described gantry in both
absorption and phase-contrast. METHODS: A phantom, containing six chemically well
defined liquids, was constructed. A tomography scan with cone-beam reconstruction
of this phantom was performed yielding the spatial distribution of the linear
attenuation coefficient MU and decrement delta of the complex refractive index.
Theoretical values of MU and delta were calculated for each liquid from tabulated
data and compared with the experimentally measured values. Additionally, a color
fused image representation is proposed to display the complementary absorption
and phase-contrast information in a single image. RESULTS: Experimental and
calculated data of the phantom agree well confirming the quantitativeness and
accuracy of the reconstructed spatial distributions of MU and delta. The proposed
color-fused image representation, which combines the complementary absorption and
phase information, considerably helps in distinguishing the individual
substances. CONCLUSIONS: The concept of grating-based phase-contrast computed
tomography (CT) can be implemented into a compact, cone-beam geometry gantry
setup. The authors believe that this work represents an important milestone in
translating phase-contrast x-ray imaging from previous proof-of-principle
experiments to first preclinical biomedical imaging applications on small-animal
models.
PMID- 22047356
TI - Technical note: further development of a resolution modification routine for the
simulation of the modulation transfer function of digital x-ray detectors.
AB - PURPOSE: This paper proposes the further development of a resolution modification
routine which is used to simulate the presampling modulation transfer function
(pMTF) of digital x-ray detectors. METHODS: It suggests a method to reconstruct
anisotropic two dimensional (2D) pMTF matrices from the experimentally measured
horizontal and vertical 1D pMTFs. In this study, the horizontal dimension of the
detector is 17.3 cm, while the vertical one is 24 cm. This matrix is multiplied
with the 2D Fourier transform of the super-sampled ideal input image to simulate
blurring. Then, the restored image is sampled to form the pixels of the digital
image. The authors suggest convolution with the comb function instead of the
rectangular function to avoid the correction with the sinc function required by
the latter. It is demonstrated that this correction is avoided when the comb
function is used. Moreover, this study suggests a way to effectively sample the
images in the case when the ratio between the "analog" pitch of the super-sampled
input image and the pixel pitch of the digital x-ray detector is a semi-integer.
RESULTS: The validation of the simulation algorithm demonstrated that when the
comb function was used the average absolute difference between the pMTF measured
from the output images and the input ones was less than 1%, while this was of 13%
when the rectangular function was used. When a sinc correction was applied in the
latter case the difference decreased again to less than 1%. CONCLUSIONS: The
developed modification routine provides the means to simulate the spatial
resolution of digital x-ray detectors under a wider range of conditions.
PMID- 22047357
TI - Improving accuracy of XRII image distortion correction using a new hybrid image
processing method: performance assessment.
AB - PURPOSE: Improving accuracy in x-ray image intensifier (XRII) image distortion
correction has clinical impact in order to apply XRII images in a variety of
clinical applications more reliably. This study aimed to develop and evaluate a
new hybrid mathematic approximation method to correct geometric distortions of
XRII images. METHODS: The proposed hybrid method integrated an MLS (moving least
squares method) and an MBA (multilevel B-spline approximation) approach (MLSMBA).
In the hybrid method, MLS is used to generate denser "virtual" data points on the
basis of sparse original data points; MBA is applied to approximate an ultimate
mapping function based on the generated and original data points. Using both
computer-simulated and real XRII images, the authors compared the image
distortion correction accuracy of the proposed method with those yielded using a
number of previously developed and currently routinely used methods. The
comparison methods include the traditional local and global approximation
methods, an approach combining both local and global approximation methods, and
an author's previously developed hybrid method by integrating MLS followed by
another traditional least-square approximation (MLSILS). The image distortion
correction accuracy was evaluated using mean-squared residual errors measured at
control and intermediate points. In addition, the impact of pincushion
distortion, sigmoidal distortion, local distortion, and control point
localization errors on these methods was tested using computer-simulated image
data. RESULTS: The experimental results using the computer-simulated data showed
that unlike the traditional local and global approximation methods that are quite
sensitive to pincushion and/or sigmoidal distortion, the MLSMBA method was
insensitive to these two types of common distortion depicted in XRII images.
Similar to the MLSILS method, sensitivity of MLSMBA to local distortion was lower
than or comparable with that of the traditional global approximation method.
Although sensitivity of MLSMBA to control point localization errors was higher
than that of the global approximation method, as long as the standard deviation
of pixel displacement errors was smaller than 0.1 pixels, the overall distortion
correction accuracy of MLSMBA remains higher than that of the other methods. By
selecting a proper cutoff radius, accuracy of MLSMBA is also higher than that of
the other methods (including MLSILS). Experiments on real XRII images yielded
similar results. For example, processing results using one XRII image showed that
residual error (0.248 +/- 0.236 pixels) of MLSMBA was smallest as compared to
that of the other methods, including two local approximation methods (0.456 +/-
0.352 pixels and 0.370 +/- 0.402 pixels), a global approximation method (0.422 +/
0.388 pixels), an approach combining local and global methods (0.389 +/- 0.386
pixels), and MLSILS (0.255 +/- 0.248 pixels). CONCLUSIONS: The MLSMBA method
could be a better choice to correct geometric distortion of raw XRII images in
the following conditions: (1) pincushion distortion, sigmoidal distortion, and
local distortion exist simultaneously in the XRII images, (2) the number of
original control points (landmarks) is limited, and (3) reusability of the
correction mapping function is required.
PMID- 22047358
TI - An adaptive regularization parameter choice strategy for multispectral
bioluminescence tomography.
AB - PURPOSE: Bioluminescence tomography (BLT) provides an effective tool for
monitoring physiological and pathological activities in vivo. However, the
measured data in bioluminescence imaging are corrupted by noise. Therefore,
regularization methods are commonly used to find a regularized solution.
Nevertheless, for the quality of the reconstructed bioluminescent source obtained
by regularization methods, the choice of the regularization parameters is
crucial. To date, the selection of regularization parameters remains challenging.
With regards to the above problems, the authors proposed a BLT reconstruction
algorithm with an adaptive parameter choice rule. METHODS: The proposed
reconstruction algorithm uses a diffusion equation for modeling the
bioluminescent photon transport. The diffusion equation is solved with a finite
element method. Computed tomography (CT) images provide anatomical information
regarding the geometry of the small animal and its internal organs. To reduce the
ill-posedness of BLT, spectral information and the optimal permissible source
region are employed. Then, the relationship between the unknown source
distribution and multiview and multispectral boundary measurements is established
based on the finite element method and the optimal permissible source region.
Since the measured data are noisy, the BLT reconstruction is formulated as l(2)
data fidelity and a general regularization term. When choosing the regularization
parameters for BLT, an efficient model function approach is proposed, which does
not require knowledge of the noise level. This approach only requests the
computation of the residual and regularized solution norm. With this knowledge,
we construct the model function to approximate the objective function, and the
regularization parameter is updated iteratively. RESULTS: First, the micro-CT
based mouse phantom was used for simulation verification. Simulation experiments
were used to illustrate why multispectral data were used rather than
monochromatic data. Furthermore, the study conducted using an adaptive
regularization parameter demonstrated our ability to accurately localize the
bioluminescent source. With the adaptively estimated regularization parameter,
the reconstructed center position of the source was (20.37, 31.05, 12.95) mm, and
the distance to the real source was 0.63 mm. The results of the dual-source
experiments further showed that our algorithm could localize the bioluminescent
sources accurately. The authors then presented experimental evidence that the
proposed algorithm exhibited its calculated efficiency over the heuristic method.
The effectiveness of the new algorithm was also confirmed by comparing it with
the L-curve method. Furthermore, various initial speculations regarding the
regularization parameter were used to illustrate the convergence of our
algorithm. Finally, in vivo mouse experiment further illustrates the
effectiveness of the proposed algorithm. CONCLUSIONS: Utilizing numerical,
physical phantom and in vivo examples, we demonstrated that the bioluminescent
sources could be reconstructed accurately with automatic regularization
parameters. The proposed algorithm exhibited superior performance than both the
heuristic regularization parameter choice method and L-curve method based on the
computational speed and localization error.
PMID- 22047359
TI - Theoretical analysis of the thread effect in helical TomoTherapy.
AB - PURPOSE: The longitudinal dose ripple on the off-axis caused by helical radiation
delivery, such as the TomoTherapy system, has been observed, and its relation
with respect to pitch has been studied with empirically found optimal pitches,
0.86/n, by Kissick et al. [Med. Phys. 32, 1414-1423 (2005)]. This ripple artifact
referred to as the thread effect is periodic in nature and is caused by various
periodic factors. In this work, the factors that cause the thread effect were
unveiled, including jaw profile divergence, the inverse square law, attenuation,
and the cone effect, and their impact on the thread effect were studied. METHODS:
Mathematical formulation for individual and combined factors were set up. Based
on theoretical analysis and simulations, optimal pitches that result in local
minima of the ripple amplitude with respect to the jaw width and off-axis
distance were identified and verified. The effectiveness of optimization in
reducing the thread effect were also studied. RESULTS: Analysis and simulation
based on the square-shaped jaw profiles well characterize the thread effect.
Simulations based on the real jaw profiles show reduced ripples and very good
agreement of optimal pitches compared with those based on the square profiles.
The optimal pitches were found to have little jaw width dependence, except for
the real jaw profile of small width (1.05 cm). The optimal pitches for the real
jaw profile of width 1.05 cm are unidentifiable except for the largest ones, due
to the relative smoothness of the jaw profile. With optimized intensity
modulation, the thread effect can be largely suppressed. For real jaw profiles,
the optimal pitches with or without dose optimization do not change much. The
numbers 0.86/n found by Kissick et al. well approximate the optimal pitches for
off-axis distance of 5 cm. However, optimal pitches are not universal for
different off-axis distances: they decrease as the off-axis distance increases.
CONCLUSIONS: The thread effect can be well explained by the proposed model.
Optimization can largely reduce the thread effect. However, an optimal pitch
reduces the ripple much easier especially when optimization is limited by many
constraints. The optimal pitches predicted by the proposed model could be used as
a reference for pitch selection regardless the tumor is at large or small off
axis distance.
PMID- 22047360
TI - Comparison of breast density measured on MR images acquired using fat-suppressed
versus nonfat-suppressed sequences.
AB - PURPOSE: To investigate the difference of MR percent breast density measured from
fat-suppressed versus nonfat-suppressed imaging sequences. METHODS: Breast
magnetic resonance imaging (MRI) with and without fat suppression was acquired
from 38 subjects. Breasts were divided into subgroups of different morphological
patterns ("central" and "intermingled" types). Breast volume, fibroglandular
tissue volume, and percent density were measured. The results were compared using
nonparametric statistical tests and regarded as significant at p < 0.05. RESULTS:
Breast volume, fibroglandular volume, and percent density between fat-suppressed
and nonfat-suppressed sequences were highly correlated. Breast volumes measured
on these two sequences were almost identical. Fibroglandular tissue volume and
percent density, however, had small (<5%) yet significant differences between the
two sequences-they were both higher on the fat-suppressed sequence. Intraobserver
variability was within 4% for both sequences and different morphological types.
The fibroglandular tissue volume measured on downsampled images showed a small
(<5%) yet significant difference. CONCLUSIONS: The measurement of breast density
made on MRI acquired using fat-suppressed and nonfat-suppressed T1W images was
about 5% difference, only slightly higher than the intraobserver variability of
3%-4%. When the density data from multiple centers were to be combined,
evaluating the degree of difference is needed to take this difference into
account.
PMID- 22047361
TI - Image quality improvement in megavoltage cone beam CT using an imaging beam line
and a sintered pixelated array system.
AB - PURPOSE: To quantify the improvement in megavoltage cone beam computed tomography
(MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line
(IBL) with a carbon electron target and a detector system equipped with a novel
sintered pixelated array (SPA) of translucent Gd(2)O(2)S ceramic scintillator.
Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment
beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si)
flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL
produces a greater fluence of keV-range photons than the TBL, to which the
detector response is more optimal, and the SPA is a more efficient scintillator
than the LFB. METHODS: A prototype IBL + SPA system was installed on a Siemens
Oncor linear accelerator equipped with the MVision(TM) image guided radiation
therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and
measuring 40 cm by 10.96 cm in the crossplane and inplane directions,
respectively, was installed in the flat panel imager. Head- and pelvis-sized
phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT
configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at
each dose was quantified using the contrast-to-noise ratio (CNR) and modulation
transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate)
cancer patients were imaged with the three imaging system configurations at
multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively
from the patient image data. RESULTS: For head and neck and pelvis-sized phantom
images, imaging doses of 3 cGy or greater, and relative electron densities of
1.09 and 1.48, the CNR average improvement factors for imaging system change of
TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were
1.63 (p < 10(- 8)), 1.64 (p < 10(- 13)), 2.66 (p < 10(- 9)), respectively. For
all imaging doses, soft tissue contrast was more easily differentiated on IBL +
SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA
thoracic images were comparable to IBL + LFB images, but less noisy than TBL +
LFB images at all imaging doses considered. The mean MTFs over all imaging doses
were comparable, at within 3%, for all imaging system configurations for both the
head- and pelvis-sized phantoms. CONCLUSIONS: Since CNR scales with the square
root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL +
SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38
and 0.37, respectively. MTFs were comparable between imaging system
configurations. IBL + SPA patient image quality was always better than that of
the TBL + LFB system and as good as or better than that of the IBL + LFB system,
for a given dose.
PMID- 22047362
TI - Learning statistical correlation for fast prostate registration in image-guided
radiotherapy.
AB - PURPOSE: In adaptive radiation therapy of prostate cancer, fast and accurate
registration between the planning image and treatment images of the patient is of
essential importance. With the authors' recently developed deformable surface
model, prostate boundaries in each treatment image can be rapidly segmented and
their correspondences (or relative deformations) to the prostate boundaries in
the planning image are also established automatically. However, the dense
correspondences on the nonboundary regions, which are important especially for
transforming the treatment plan designed in the planning image space to each
treatment image space, are remained unresolved. This paper presents a novel
approach to learn the statistical correlation between deformations of prostate
boundary and nonboundary regions, for rapidly estimating deformations of the
nonboundary regions when given the deformations of the prostate boundary at a new
treatment image. METHODS: The main contributions of the proposed method lie in
the following aspects. First, the statistical deformation correlation will be
learned from both current patient and other training patients, and further
updated adaptively during the radiotherapy. Specifically, in the initial
treatment stage when the number of treatment images collected from the current
patient is small, the statistical deformation correlation is mainly learned from
other training patients. As more treatment images are collected from the current
patient, the patient-specific information will play a more important role in
learning patient-specific statistical deformation correlation to effectively
reflect prostate deformation of the current patient during the treatment.
Eventually, only the patient-specific statistical deformation correlation is used
to estimate dense correspondences when a sufficient number of treatment images
have been acquired from the current patient. Second, the statistical deformation
correlation will be learned by using a multiple linear regression (MLR) model,
i.e., ridge regression (RR) model, which has the best prediction accuracy than
other MLR models such as canonical correlation analysis (CCA) and principal
component regression (PCR). RESULTS: To demonstrate the performance of the
proposed method, we first evaluate its registration accuracy by comparing the
deformation field predicted by our method with the deformation field estimated by
the thin plate spline (TPS) based correspondence interpolation method on 306
serial prostate CT images of 24 patients. The average predictive error on the
voxels around 5 mm of prostate boundary is 0.38 mm for our method of RR-based
correlation model. Also, the corresponding maximum error is 2.89 mm. We then
compare the speed for deformation interpolation by different methods. When
considering the larger region of interest (ROI) with the size of 512 * 512 * 61,
our method takes 24.41 seconds to interpolate the dense deformation field while
TPS method needs 6.7 minutes; when considering a small ROI (surrounding prostate)
with size of 112 * 110 * 93, our method takes 1.80 seconds, while TPS method
needs 25 seconds. CONCLUSIONS: Experimental results show that the proposed method
can achieve much faster registration speed yet with comparable registration
accuracy, compared to the TPS-based correspondence (or deformation) interpolation
approach.
PMID- 22047363
TI - The correlation of tissue motion within the lung: implications on fiducial based
treatments.
AB - In radiation therapy many motion management and alignment techniques rely on the
accuracy of an internal fiducial acting as a surrogate for target motion within
the lung. Although fiducials are routinely used as surrogates for tumor motion,
the extent to which varying spatial locations in the lung move similarly to other
locations has yet to be quantitatively analyzed. In an attempt to analyze the
motion correlation throughout the lung, ten primary lung cancer patients
underwent IRB-approved 4DCT scans in the supine position. Deformable registration
produced motion vectors for each voxel between exhalation and inhalation.
Modeling was performed for each vector and all surrounding vectors within the
lung in order to determine the mean 3D Euclidean distance necessary for an
implanted fiducial to correlate with surrounding tissue motion to within 3 mm
(left lower: 1.7 cm, left upper: 2.1 cm, right lower 1.6 cm, and right upper 2.9
cm). No general implantation rule of where to position a fiducial with respect to
the tumor was found as the motion is highly patient and lobe specific.
Correlation maps are presented showcasing spatial anisotropy of the motion of
tissue surrounding the tumor.
PMID- 22047364
TI - Improving suspicious breast lesion characterization using semi-automatic lesion
fractional volume washout kinetic analysis.
AB - PURPOSE: Although breast dynamic contrast-enhanced magnetic resonance imaging
(DCE-MRI) demonstrates high sensitivity for malignant tumor detection, a major
limitation is the relative low specificity, resulting in many false-positive
diagnoses of suspicious lesions (BI-RADS assessment of 4 or 5) in clinical
practice and consequently producing a relatively low positive predictive value
(PPV) for biopsies. The most enhanced areas in the malignant tumors show a
typical washout (WO) kinetic feature for the postcontrast signal intensity time
courses and also correlate with microvessel density. Benign proliferative breast
diseases can also produce the WO curve, yielding an equivocal kinetic behavior
for the benign lesions and rendering their diagnoses as suspicious lesions in
clinical practice. Considering that tumor angiogenesis is essential to an
aggressive cancer tumor growth, the authors hypothesize that the WO volume
fraction, i.e., the total volume of the WO voxels that demonstrate the WO curve
within the tumor, is relatively large for malignant tumors in comparison to that
for benign lesions. In this study, the authors present a lesion fractional volume
WO kinetic analysis for improving the characterization of suspicious breast
lesions. METHODS: A method to automatically detect the boundary of a manually
selected contrast-enhanced lesion was introduced and tested, utilizing the signal
intensity difference between the contrast-enhanced lesion and its surrounding
tissues. The kinetic features of the postcontrast signal intensity time courses
were quantitatively analyzed voxel-by-voxel with emphasis on the examination of
the WO behavior. The WO volume fraction relative to the whole lesion volume was
introduced and tested as a biomarker for improving the characterization of
suspicious breast lesions. The sample for this test consisted of 28 suspicious
lesions with correlative histopathology reports available. The lesions included
10 malignant tumors and 18 benign lesions, yielding a 35.7% PPV of the biopsies.
RESULTS: The semi-automatic method produced an objective volume of interest for
each lesion with voxelwise-quantified kinetic features. With an optimal choice of
kinetic analysis, the mean and standard deviation of the WO volume fraction were
59.1 +/- 13.1 (%) with the range from 41.0% to 80.7% for the malignant tumors and
31.4 +/- 20.5 (%) with the range between 3.3% and 71.6% for the benign lesions,
respectively. The WO volume fraction was significantly larger (p < 0.0004) for
the malignant tumors than for the benign lesions. While maintaining the same
sensitivity for malignant tumors, using the WO volume fraction as an additional
biomarker would characterize 14 out of the 18 benign lesions as benign,
potentially resulting in an 100% improvement rate in the PPV of the biopsies
(from 35.7% to 71.4%) and consequently a 77.8% reduction rate in potentially
unnecessary biopsies (from 18 to 4). CONCLUSIONS: The significantly larger WO
volume fraction for the malignant tumors was probably related to the increased
vascularity associated with tumor angiogenesis. The results suggest that the WO
volume fraction biomarker has potential to improve the computer-based assessment
of breast MRI by greatly increasing the PPV of breast biopsies and potentially
significantly reducing the number of unnecessary biopsies without compromising
sensitivity.
PMID- 22047365
TI - The effect of errors in segmented attenuation maps on PET quantification.
AB - PURPOSE: Accurate attenuation correction is important for PET quantification.
Often, a segmented attenuation map is used, especially in MRI-based attenuation
correction. As deriving the attenuation map from MRI images is difficult,
different errors can be present in the segmented attenuation map. The goal of
this paper is to determine the effect of these errors on quantification. METHODS:
The authors simulated the digital XCAT phantom using the GATE Monte Carlo
simulation framework and a model of the Philips Gemini TF. A whole body scan was
simulated, spanning an axial field of view of 70 cm. A total of fifteen lesions
were placed in the lung, liver, spine, colon, prostate, and femur. The acquired
data were reconstructed with a reference attenuation map and with different
attenuation maps that were modified to reflect common segmentation errors. The
quantitative difference between reconstructed images was evaluated. RESULTS:
Segmentation into five tissue classes, namely cortical bone, spongeous bone, soft
tissue, lung, and air yielded errors below 5%. Large errors were caused by
ignoring lung tissue (up to 45%) or cortical bone (up to 17%). The interpatient
variability of lung attenuation coefficients can lead to errors of 10% and more.
Up to 20% tissue misclassification from bone to soft tissue yielded errors below
5%. The same applies for up to 10% misclassification from lung to air.
CONCLUSIONS: When using a segmented attenuation map, at least five different
tissue types should be considered: cortical bone, spongeous bone, soft tissue,
lung, and air. Furthermore, the interpatient variability of lung attenuation
coefficients should be taken into account. Limited misclassification from bone to
soft tissue and from lung to air is acceptable, as these do not lead to relevant
errors.
PMID- 22047366
TI - Reference dosimetry for helical tomotherapy: practical implementation and a
multicenter validation.
AB - PURPOSE: The aim of this study was to implement a protocol for reference
dosimetry in tomotherapy and to validate the beam output measurements with an
independent dosimetry system. METHODS: Beam output was measured at the reference
depth of 10 cm in water for the following three cases: (1) a 5 * 10 cm(2) static
machine specific reference field (MSR), (2) a rotational 5 * 10 cm(2) field
without modulation and no tabletop in the beam, (3) a plan class specific
reference (PCSR) field defined as a rotational homogeneous dose delivery to a
cylindrical shaped target volume: plan with modulation and table-top movement.
The formalism for reference dosimetry of small and nonstandard fields
[Med.Phys.35: 5179-5186, 2008] and QA recommendations [Med.Phys.37: 4817-4853,
2010] were adopted in the dose measurement protocol. All ionization chamber
measurements were verified independently using alanine/EPR dosimetry. As a pilot
study, the beam output was measured on tomotherapy Hi-art systems at three other
centers and directly compared to the centers specifications and to alanine
dosimetry. RESULTS: For the four centers, the mean static output at a depth of 10
cm in water and SAD = 85 cm, measured with an A1SL chamber following the TG-148
report was 6.238 Gy/min +/- 0.058 (1 SD); the rotational output was 6.255 Gy/min
+/- 0.069 (1 SD). The dose stated by the center was found in good agreement with
the measurements of the visiting team: D(center)/D(visit) = 1.000 +/- 0.003 (1
SD). The A1SL chamber measurements were all in good agreement with Alanine/EPR
dosimetry. Going from the static reference field to the rotational / non
modulated field the dose rate remains constant within 0.2% except for one center
where a deviation of 1.3% was detected. CONCLUSIONS: Following the TG-148 report,
beam output measurements in water at the reference depth using a local protocol,
as developed at different centers, was verified. The measurements were found in
good agreement with alanine/EPR dosimetry. The presented methodology may provide
a good concept for reference dosimetry.
PMID- 22047367
TI - Scatter correction for full-fan volumetric CT using a stationary beam blocker in
a single full scan.
AB - PURPOSE: Applications of volumetric CT (VCT) are hampered by shading and
streaking artifacts in the reconstructed images. These artifacts are mainly due
to strong x-ray scatter signals accompanied with the large illumination area
within one projection, which lead to CT number inaccuracy, image contrast loss
and spatial nonuniformity. Although different scatter correction algorithms have
been proposed in literature, a standard solution still remains unclear.
Measurement-based methods use a beam blocker to acquire scatter samples. These
techniques have unrivaled advantages over other existing algorithms in that they
are simple and efficient, and achieve high scatter estimation accuracy without
prior knowledge of the imaged object. Nevertheless, primary signal loss is
inevitable in the scatter measurement, and multiple scans or moving the beam
blocker during data acquisition are typically employed to compensate for the
missing primary data. In this paper, we propose a new measurement-based scatter
correction algorithm without primary compensation for full-fan VCT. An accurate
reconstruction is obtained with one single-scan and a stationary x-ray beam
blocker, two seemingly incompatible features which enable simple and efficient
scatter correction without increase of scan time or patient dose. METHODS: Based
on the CT reconstruction theory, we distribute the blocked data over the
projection area where primary signals are considered approximately redundant in a
full scan, such that the CT image quality is not degraded even with primary loss.
Scatter is then accurately estimated by interpolation and scatter-corrected CT
images are obtained using an FDK-based reconstruction algorithm. RESULTS: The
proposed method is evaluated using two phantom studies on a tabletop CBCT system.
On the Catphan(c)600 phantom, our approach reduces the reconstruction error from
207 Hounsfield unit (HU) to 9 HU in the selected region of interest, and improves
the image contrast by a factor of 2.0 in the high-contrast regions. On an
anthropomorphic head phantom, the reconstruction error is reduced from 97 HU to 6
HU in the soft tissue region and image spatial nonuniformity decreases from 27%
to 5% after correction. CONCLUSIONS: Our method inherits the main advantages of
measurement-based methods while avoiding their shortcomings. It has the potential
to become a practical scatter correction solution widely implementable on
different VCT systems.
PMID- 22047368
TI - Dynamic MLC leaf sequencing for integrated linear accelerator control systems.
AB - PURPOSE: Leaf positions for dynamic multileaf collimator (DMLC) intensity
modulated radiation therapy must be closely synchronized with MU delivery. For
the Varian C3 series MLC controller, if the planned trajectory (leaf position vs.
MU) requires velocities exceeding the capability of the MLC, the leaves fall
behind the planned positions, causing the controller to momentarily hold the beam
and thereby introduce dosimetric errors. We investigated the merits of a new
commercial linear accelerator, TrueBeamTM, that integrates MLC control with
prospective dose rate modulation. If treatment is delivered at dose rates so high
that leaves would fall behind, the controller reduces the dose rate such that
harmony between MU and leaf position is preserved. METHODS: For three sets of
DMLC leaf trajectories, point doses and two-dimensional dose distributions were
measured in phantom using an ionization chamber and film, respectively. The first
set, delivered using both a TrueBeamTM and a conventional C3 controller,
comprised a single leaf bank closing at planned velocities of 2.4, 7.1, and 14
cm/s. The maximum achievable leaf velocity for both systems was 3 cm/s. The
remaining two sets were derived from clinical fluence maps using a commercial
treatment planning system for a range of planned dose rates and were delivered
using TrueBeamTM set to the maximum dose rate, 600 MU/min. Generating
trajectories using a planned dose rate that is lower than the delivery dose rate
effectively increased the leaf velocity constraint used by the planning system
for trajectory calculation. The second set of leaf trajectories was derived from
two fluence maps containing regions of zero fluence obtained from representative
beams of two different patient treatment plans. The third set was obtained from
all nine fields of a head and neck treatment plan. For the head and neck plan,
dose-volume histograms of the spinal cord and target for each planned dose rate
were obtained. RESULTS: For the single closing leaf bank trajectories, the
TrueBeamTM control system reduced the dose rate such that the leaf velocity was
less than the maximum. Dose deviations relative to the 2.4 cm/s trajectory were
less than 3%. For the conventional controller, the leaves repeatedly fell behind
the planned positions until the beam hold threshold was reached, resulting in
deviations of up to 19% relative to the 2.4 cm/s trajectory. For the two clinical
fluence maps, reducing the planned dose rate reduced the dose in the zero fluence
regions by 15% and 24% and increased the delivery time by 5 s and 14 s. No
significant differences were noted in the high and intermediate dose regions
measured using film. The DVHs for the head and neck plan showed a 10% reduction
in cord dose for 20 MU/min relative to 600 MU/min sequencing dose rate, which was
confirmed by measurement. No difference in target DVHs were observed. The
reduction in cord dose increased total treatment time by 1.8 min. CONCLUSIONS:
Leaf sequencing algorithms for integrated control systems should be modified to
reflect the reduced importance of maximum leaf velocity for accurate dose
delivery.
PMID- 22047369
TI - A comparison of postimplant dosimetry for (103)Pd versus (131)Cs seeds on a
retrospective series of PBSI patients.
AB - PURPOSE: Permanent breast seed implantation (PBSI) is an accelerated partial
breast irradiation technique performed using stranded (103)Pd radioactive seeds
(average energy of 21 keV, 16.97 day half-life). Since 2004, (131)Cs
brachytherapy sources have become clinically available. The (131)Cs radionuclide
has a higher energy (average energy of 30 keV) and a shorter half-life (9.7 days)
than (103)Pd. The purpose of this study was to determine whether or not there are
dosimetric benefits to using (131)Cs brachytherapy seeds for PBSI. METHODS: The
prescribed dose for PBSI using (103)Pd is 90 Gy, which was adjusted for (131)Cs
implants to account for the shorter half-life. A retrospective cohort of 30
patients, who have already undergone a (103)Pd implant, was used for this study.
The treatments were planned using the Variseed treatment planning system. The air
kerma strength of the (131)Cs seeds was adjusted in all preimplantation treatment
plans so that the V(100) (the volume within the target that receives 100% or more
of the prescribed dose) were equivalent at time of implantation. Two month follow
up CT scans were available for all 30 patients and each patient was reevaluated
using (131)Cs seeds. The postimplant dosimetric parameters were compared using a
two tailed t-test. RESULTS: The prescribed dose for (131)Cs was calculated to be
77 Gy; this dose would have the same biological effect as a PBSI implant with
(103)Pd of 90 Gy. The activities of the (131)Cs sources were adjusted to an
average of 2.2 +/- 0.8 U for (131)Cs compared to 2.5 +/- 1.1 U for (103)Pd in
order to get an equivalent V(100) as the (103)Pd preimplants. While the use of
(131)Cs significantly reduces the preimplant V(200) (the volume within the target
that receives 200% or more of the prescribed dose) compared to (103)Pd by 13.5 +/
9.0%, the reduction observed on the 2 month postimplant plan was 12.4 +/- 5.1%
which accounted for seed motion, implantation inaccuracies and tissue changes.
This translates into an absolute reduction of 4.1 cm(3) of tissue receiving 200%
of the dose. CONCLUSIONS: This analysis of 30 early stage breast cancer patients
who underwent the PBSI procedure shows that there is a theoretical dosimetric
advantage to using (131)Cs. However, in a realistic implant that will have seed
misplacements and tissue changes, the use of (131)Cs may not result in any
clinically significant benefit.
PMID- 22047370
TI - Statistical variability and confidence intervals for planar dose QA pass rates.
AB - PURPOSE: The most common metric for comparing measured to calculated dose, such
as for pretreatment quality assurance of intensity-modulated photon fields, is a
pass rate (%) generated using percent difference (%Diff), distance-to-agreement
(DTA), or some combination of the two (e.g., gamma evaluation). For many
dosimeters, the grid of analyzed points corresponds to an array with a low areal
density of point detectors. In these cases, the pass rates for any given
comparison criteria are not absolute but exhibit statistical variability that is
a function, in part, on the detector sampling geometry. In this work, the authors
analyze the statistics of various methods commonly used to calculate pass rates
and propose methods for establishing confidence intervals for pass rates obtained
with low-density arrays. METHODS: Dose planes were acquired for 25 prostate and
79 head and neck intensity-modulated fields via diode array and electronic portal
imaging device (EPID), and matching calculated dose planes were created via a
commercial treatment planning system. Pass rates for each dose plane pair (both
centered to the beam central axis) were calculated with several common comparison
methods: %Diff/DTA composite analysis and gamma evaluation, using absolute dose
comparison with both local and global normalization. Specialized software was
designed to selectively sample the measured EPID response (very high data
density) down to discrete points to simulate low-density measurements. The
software was used to realign the simulated detector grid at many simulated
positions with respect to the beam central axis, thereby altering the low-density
sampled grid. Simulations were repeated with 100 positional iterations using a 1
detector/cm(2) uniform grid, a 2 detector/cm(2) uniform grid, and similar random
detector grids. For each simulation, %/DTA composite pass rates were calculated
with various %Diff/DTA criteria and for both local and global %Diff normalization
techniques. RESULTS: For the prostate and head/neck cases studied, the pass rates
obtained with gamma analysis of high density dose planes were 2%-5% higher than
respective %/DTA composite analysis on average (ranging as high as 11%),
depending on tolerances and normalization. Meanwhile, the pass rates obtained via
local normalization were 2%-12% lower than with global maximum normalization on
average (ranging as high as 27%), depending on tolerances and calculation method.
Repositioning of simulated low-density sampled grids leads to a distribution of
possible pass rates for each measured/calculated dose plane pair. These
distributions can be predicted using a binomial distribution in order to
establish confidence intervals that depend largely on the sampling density and
the observed pass rate (i.e., the degree of difference between measured and
calculated dose). These results can be extended to apply to 3D arrays of
detectors, as well. CONCLUSIONS: Dose plane QA analysis can be greatly affected
by choice of calculation metric and user-defined parameters, and so all pass
rates should be reported with a complete description of calculation method. Pass
rates for low-density arrays are subject to statistical uncertainty (vs. the high
density pass rate), but these sampling errors can be modeled using statistical
confidence intervals derived from the sampled pass rate and detector density.
Thus, pass rates for low-density array measurements should be accompanied by a
confidence interval indicating the uncertainty of each pass rate.
PMID- 22047371
TI - Task-based weights for photon counting spectral x-ray imaging.
AB - PURPOSE: To develop a framework for taking the spatial frequency composition of
an imaging task into account when determining optimal bin weight factors for
photon counting energy sensitive x-ray systems. A second purpose of the
investigation is to evaluate the possible improvement compared to using pixel
based weights. METHODS: The Fourier based approach of imaging performance and
detectability index d' is applied to pulse height discriminating photon counting
systems. The dependency of d' on the bin weight factors is made explicit, taking
into account both differences in signal and noise transfer characteristics across
bins and the spatial frequency dependency of interbin correlations from
reabsorbed scatter. Using a simplified model of a specific silicon detector, d'
values for a high and a low frequency imaging task are determined for optimal
weights and compared to pixel based weights. RESULTS: The method successfully
identifies bins where a large point spread function degrades detection of high
spatial frequency targets. The method is also successful in determining how to
downweigh highly correlated bins. Quantitative predictions for the simplified
silicon detector model indicate that improvements in the detectability index when
applying task-based weights instead of pixel based weights are small for high
frequency targets, but could be in excess of 10% for low frequency tasks where
scatter-induced correlation otherwise degrade detectability. CONCLUSIONS: The
proposed method makes the spatial frequency dependency of complex correlation
structures between bins and their effect on the system detective quantum
efficiency easier to analyze and allows optimizing bin weights for given imaging
tasks. A potential increase in detectability of double digit percents in silicon
detector systems operated at typical CT energies (100 kVp) merits further
evaluation on a real system. The method is noted to be of higher relevance for
silicon detectors than for cadmium (zink) telluride detectors.
PMID- 22047372
TI - Radiochromic film dosimetry of HDR (192)Ir source radiation fields.
AB - PURPOSE: A radiochromic film based dosimetry system for high dose rate (HDR)
Iridium-192 brachytherapy source was described. A comparison between calibration
curves established in water and Solid WaterTM was provided. METHODS: Pieces of
EBT-2 model GAFCHROMICTM film were irradiated in both water and Solid WaterTM
with HDR (192)Ir brachytherapy source in a dose range from 0 to 50 Gy. Responses
of EBT-2 GAFCHROMICTM film were compared for irradiations in water and Solid
WaterTM by scaling the dose between media through Monte Carlo calculated
conversion factor for both setups. To decrease uncertainty in dose delivery due
to positioning of the film piece with respect to the radiation source, traceable
calibration irradiations were performed in a parallel-opposed beam setup.
RESULTS: The EBT-2 GAFCHROMICTM film based dosimetry system described in this
work can provide an overall one-sigma dose uncertainty of 4.12% for doses above 1
Gy. The ratio of dose delivered to the sensitive layer of the film in water to
the dose delivered to the sensitive layer of the film in Solid WaterTM was
calculated using Monte Carlo simulations to be 0.9941 +/- 0.0007. CONCLUSIONS: A
radiochromic film based dosimetry system using only the green color channel of a
flatbed document scanner showed superior precision if used alone in a dose range
that extends up to 50 Gy, which greatly decreases the complexity of work. In
addition, Solid WaterTM material was shown to be a viable alternative to water in
performing radiochromic film based dosimetry with HDR (192)Ir brachytherapy
sources.
PMID- 22047373
TI - Radiation dose reduction to the breast in thoracic CT: comparison of bismuth
shielding, organ-based tube current modulation, and use of a globally decreased
tube current.
AB - PURPOSE: The purpose of this work was to evaluate dose performance and image
quality in thoracic CT using three techniques to reduce dose to the breast:
bismuth shielding, organ-based tube current modulation (TCM) and global tube
current reduction. METHODS: Semi-anthropomorphic thorax phantoms of four
different sizes (15, 30, 35, and 40 cm lateral width) were used for dose
measurement and image quality assessment. Four scans were performed on each
phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2)
scan with bismuth breast shield of an appropriate thickness; (3) scan with organ
based TCM; and (4) scan with a global reduction in tube current chosen to match
the dose reduction from bismuth shielding. Dose to the breast was measured with
an ion chamber on the surface of the phantom. Image quality was evaluated by
measuring the mean and standard deviation of CT numbers within the lung and heart
regions. RESULTS: Compared to the reference scan, dose to the breast region was
decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and
by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ
based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30,
35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose
by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In
phantoms of all four sizes, image noise was increased in both the lung and heart
regions with bismuth shielding. No significant increase in noise was observed
with organ-based TCM. Decreasing tube current globally led to similar noise
increases as bismuth shielding. Streak and beam hardening artifacts, and a
resulting artifactual increase in CT numbers, were observed for scans with
bismuth shields, but not for organ-based TCM or global tube current reduction.
CONCLUSIONS: Organ-based TCM produces dose reduction to the breast similar to
that achieved with bismuth shielding for both pediatric and adult phantoms.
However, organ-based TCM does not affect image noise or CT number accuracy, both
of which are adversely affected by bismuth shielding. Alternatively, globally
decreasing the tube current can produce the same dose reduction to the breast as
bismuth shielding, with a similar noise increase, yet without the streak
artifacts and CT number errors caused by the bismuth shields. Moreover, globally
decreasing the tube current reduces the dose to all tissues scanned, not simply
to the breast.
PMID- 22047374
TI - Zonal segmentation of prostate using multispectral magnetic resonance images.
AB - PURPOSE: To investigate the performance of a new method of automatic segmentation
of prostatic multispectral magnetic resonance images into two zones: the
peripheral zone and the central gland. METHODS: The proposed method is based on a
modified version of the evidential C-means clustering algorithm. The evidential C
means optimization process was modified to introduce spatial neighborhood
information. A priori knowledge of the prostate's zonal morphology was modeled as
a geometric criterion and used as an additional data source to enhance the
differentiation of the two zones. RESULTS: Thirty-one clinical magnetic resonance
imaging series were used to validate the method, and interobserver variability
was taken into account in assessing its accuracy. The mean Dice Similarity
Coefficient was 89% for the central gland and 80% for the peripheral zone, as
validated by a consensus from expert radiologist segmentation. CONCLUSIONS: The
method was statistically insensitive to variations in patient age, prostate
volume and the presence of tumors, which increases its feasibility in a clinical
context.
PMID- 22047375
TI - Impact of leaf motion constraints on IMAT plan quality, deliver accuracy, and
efficiency.
AB - PURPOSE: Intensity modulated arc therapy (IMAT) is a radiation therapy delivery
technique that combines the efficiency of arc based delivery with the dose
painting capabilities of intensity modulated radiation therapy (IMRT). A key
challenge in developing robust inverse planning solutions for IMAT is the need to
account for the connectivity of the beam shapes as the gantry rotates from one
beam angle to the next. To overcome this challenge, inverse planning solutions
typically impose a leaf motion constraint that defines the maximum distance a
multileaf collimator (MLC) leaf can travel between adjacent control points. The
leaf motion constraint ensures the deliverability of the optimized plan, but it
also impacts the plan quality, the delivery accuracy, and the delivery
efficiency. In this work, the authors have studied leaf motion constraints in
detail and have developed recommendations for optimizing the balance between plan
quality and delivery efficiency. METHODS: Two steps were used to generate
optimized IMAT treatment plans. The first was the direct machine parameter
optimization (DMPO) inverse planning module in the Pinnacle(3) planning system.
Then, a home-grown arc sequencer was applied to convert the optimized intensity
maps into deliverable IMAT arcs. IMAT leaf motion constraints were imposed using
limits of between 1 and 30 mm/deg. Dose distributions were calculated using the
convolution/superposition algorithm in the Pinnacle(3) planning system. The IMAT
plan dose calculation accuracy was examined using a finer sampling calculation
and the quality assurance verification. All plans were delivered on an Elekta
Synergy with an 80-leaf MLC and were verified using an IBA MatriXX 2D ion chamber
array inserted in a MultiCube solid water phantom. RESULTS: The use of a more
restrictive leaf motion constraint (less than 1-2 mm/deg) results in inferior
plan quality. A less restrictive leaf motion constraint (greater than 5 mm/deg)
results in improved plan quality but can lead to less accurate dose distribution
as evidenced by increasing discrepancies between the planned and the delivered
doses. For example, the results from our patient-specific quality assurance
measurements demonstrated that the average gamma analysis passing rate decreased
from 98% to 80% when the allowable leaf motion increased from 3 to 20 mm/deg.
Larger leaf motion constraints also led to longer treatment delivery times (2 to
4 folds) due to the additional MLC leaf motion. CONCLUSIONS: Leaf motion
constraints significantly impact IMAT plans in terms of plan quality, delivery
accuracy, and delivery efficiency with the impact magnified for more complex
cases. Our studies indicate that a leaf motion constraint of 2 to 3 mm/deg of
gantry rotation can provide an optimal balance between plan quality, delivery
accuracy, and efficiency.
PMID- 22047376
TI - Analysis of shear strain imaging for classifying breast masses: finite element
and phantom results.
AB - PURPOSE: Features extracted from axial-shear strain images of breast masses have
been previously utilized to differentiate and classify benign from malignant
breast masses. In this paper, we compare shear strain patterns exhibited by both
the full-shear (axial and lateral component) versus only the axial-shear strain
component for differentiating between bound masses (malignant) when compared to
unbound masses (benign). METHODS: We examine different breast mass
characteristics such as mass shape, asymmetric location of masses, stiffness
variations, and mass bonding characteristics to background tissue to assess their
impact on shear strain patterns generated due to a uniaxial applied deformation.
Two-dimensional finite element simulations of both circular and elliptical
inclusions embedded within a uniform background were utilized. Different degrees
of bonding were characterized using friction coefficient values ranging from 0.01
to 100 denoting loosely bound to firmly bound masses. Single-inclusion tissue
mimicking phantoms mimicking firmly bound and loosely bound ellipsoidal masses
oriented at four different angles to the applied deformation were studied to
corroborate the mass differentiation performance. RESULTS: Our results indicate
that the normalized axial-shear strain and full-shear strain area features are
larger for bound when compared to unbound masses. A higher stiffness ratio or
contrast between the inclusion and background also improves differentiation.
Larger applied deformations reduce the discrimination performance for masses with
friction coefficients lower than 0.4, due to increased mass slippage with applied
deformations. Potential errors with the use of these features would occur for
unbound inclusions at larger applied deformations and for asymmetric mass
positions within the background normal tissue. CONCLUSIONS: Finite element and
tissue-mimicking phantom results demonstrate the feasibility of utilizing both
the normalized axial-shear and full-shear strain area features to classify breast
masses. Differentiation between bound or unbound masses was not affected by the
mass size or shape for masses where the applied deformation is normal to the mass
surface. Shear strain patterns vary significantly especially within unbound
masses, when the mass surface is not normal to the applied deformation.
Discrimination performance for unbound masses was improved by utilizing only the
normalized shear strain area patterns located outside the mass as illustrated in
this paper.
PMID- 22047377
TI - Automated bone removal in CT angiography: comparison of methods based on single
energy and dual energy scans.
AB - PURPOSE: To evaluate dual energy based methods for bone removal in computed
tomography angiography (CTA) images and compare these with single energy based
methods that use an additional, nonenhanced, CT scan. METHODS: Four different
bone removal methods were applied to CT scans of an anthropomorphic thorax
phantom, acquired with a second generation dual source CT scanner. The methods
differed by the way information on the presence of bone was obtained (either by
using an additional, nonenhanced scan or by scanning with two tube voltages at
the same time) and by the way the bone was removed from the CTA images (either by
masking or subtracting the bone). The phantom contained parts which mimic vessels
of various diameters in direct contact with bone. Both a quantitative and
qualitative analysis of image quality after bone removal was performed. Image
quality was quantified by the contrast-to-noise ratio (CNR) normalized to the
square root of the dose (CNRD). At locations where vessels touch bone, the
quality of the bone removal and the vessel preservation were visually assessed.
The dual energy based methods were assessed with and without the addition of a
0.4 mm tin filter to the high voltage x-ray tube filtration. For each bone
removal method, the dose required to obtain a certain CNR after bone removal was
compared with the dose of a reference scan with the same CNR but without
automated bone removal. The CNRD value of the reference scan was maximized by
choosing the lowest tube voltage available. RESULTS: All methods removed the bone
completely. CNRD values were higher for the masking based methods than for the
subtraction based methods. Single energy based methods had a higher CNRD value
than the corresponding dual energy based methods. For the subtraction based dual
energy method, tin filtration improved the CNRD value with approximately 50%. For
the masking based dual energy method, it was easier to differentiate between
iodine and bone when tin filtration was applied. The CNRD value decreased only
with 4% in that case. Compared to the dual scan based methods, the dual energy
based methods had the advantage that only a single scan was made without the need
of image registration. This might be easier to implement in clinical practice.
Vessel preservation was better with bone subtraction than with bone masking.
Smaller vessels were completely occluded by the bone mask. None of the bone
removal methods was dose neutral. CONCLUSIONS: In general, dual scan based
methods that use the lowest tube voltage available, have a higher CNR than the
dual energy based approaches at the same dose level. Tin filtration improves the
ability to differentiate between iodine and bone for the dual energy based
masking method. In clinical practice, the advantages of the dual energy masking
method might outweigh its disadvantage of a slightly higher dose penalty compared
to the conventional dual scan masking method.
PMID- 22047378
TI - K-space reconstruction with anisotropic kernel support (KARAOKE) for ultrafast
partially parallel imaging.
AB - PURPOSE: Partially parallel imaging (PPI) greatly accelerates MR imaging by using
surface coil arrays and under-sampling k-space. However, the reduction factor (R)
in PPI is theoretically constrained by the number of coils (N(C)). A
symmetrically shaped kernel is typically used, but this often prevents even the
theoretically possible R from being achieved. Here, the authors propose a kernel
design method to accelerate PPI faster than R = N(C). METHODS: K-space data
demonstrates an anisotropic pattern that is correlated with the object itself and
to the asymmetry of the coil sensitivity profile, which is caused by coil
placement and B(1) inhomogeneity. From spatial analysis theory, reconstruction of
such pattern is best achieved by a signal-dependent anisotropic shape kernel. As
a result, the authors propose the use of asymmetric kernels to improve k-space
reconstruction. The authors fit a bivariate Gaussian function to the local signal
magnitude of each coil, then threshold this function to extract the kernel
elements. A perceptual difference model (Case-PDM) was employed to quantitatively
evaluate image quality. RESULTS: A MR phantom experiment showed that k-space
anisotropy increased as a function of magnetic field strength. The authors tested
a K-spAce Reconstruction with AnisOtropic KErnel support ("KARAOKE") algorithm
with both MR phantom and in vivo data sets, and compared the reconstructions to
those produced by GRAPPA, a popular PPI reconstruction method. By exploiting k
space anisotropy, KARAOKE was able to better preserve edges, which is
particularly useful for cardiac imaging and motion correction, while GRAPPA
failed at a high R near or exceeding N(C). KARAOKE performed comparably to GRAPPA
at low Rs. CONCLUSIONS: As a rule of thumb, KARAOKE reconstruction should always
be used for higher quality k-space reconstruction, particularly when PPI data is
acquired at high Rs and/or high field strength.
PMID- 22047379
TI - Dosimetry of a new P-32 ophthalmic applicator.
AB - PURPOSE: The potential of P-32 ophthalmic applicator irradiation after pterygium
excision has been demonstrated as an alternative to Sr/Y-90 irradiation. This
study aimed to provide the clinical dosimetry for this new applicator. METHODS:
The prototype of a cylindrical P-32 applicator was fabricated according to the
Monte Carlo (MC)-based design study. At a nominal activity of 6 mCi (0.22 GBq),
the absorbed dose rate at the front surface (i.e., reference dose rate) was
measured by using an extrapolation ionization chamber (EC). The radiochromic film
(RCF) was also used to measure the reference dose, axial depth dose distributions
and transaxial dose profiles at various depths in water. RESULTS: The reference
dose rate was 3.89 +/- 0.14 cGy/s for EC and 3.84 +/- 0.25 cGy/s for RCF. The
depth dose rate was reduced approximately by an order of magnitude for every 2 mm
depth in water. Measured depth doses in depths of 0.5-2.5 mm agreed with Monte
Carlo data within +/-3%. Due to nonuniform absorption of P-32 into an absorbent
disk, the dose profiles were not symmetric and decreased more rapidly toward the
periphery than those predicted by the MC. The authors confirmed no leakage of P
32 activities and negligible exposure rate around the hand grip of the
applicator. CONCLUSIONS: The P-32 applicator can deliver therapeutic doses to the
surface of the conjunctiva, while sparing the lens better than Sr/Y-90
applicators. The doses at any points from the P-32 applicator could be calculated
by using the measured dosimetry data. They also confirmed no leakage of the
source, reliable integrity of the applicator, and negligible exposure level
around the hand grip of the applicator. However, due to a possibility of
nonuniform distributions of P-32 in an absorbent disk, measuring dose profiles as
well as the reference dose rate for every new applicator would be recommended.
PMID- 22047380
TI - Imaging of moving fiducial markers during radiotherapy using a fast, efficient
active pixel sensor based EPID.
AB - PURPOSE: The purpose of this work was to investigate the use of an experimental
complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) for
tracking of moving fiducial markers during radiotherapy. METHODS: The APS has an
active area of 5.4 * 5.4 cm and maximum full frame read-out rate of 20 frame s(
1), with the option to read out a region-of-interest (ROI) at an increased rate.
It was coupled to a 4 mm thick ZnWO4 scintillator which provided a quantum
efficiency (QE) of 8% for a 6 MV x-ray treatment beam. The APS was compared with
a standard iViewGT flat panel amorphous Silicon (a-Si) electronic portal imaging
device (EPID), with a QE of 0.34% and a frame-rate of 2.5 frame s(-1). To
investigate the ability of the two systems to image markers, four gold cylinders
of length 8 mm and diameter 0.8, 1.2, 1.6, and 2 mm were placed on a motion
platform. Images of the stationary markers were acquired using the APS at a frame
rate of 20 frame s(-1), and a dose-rate of 143 MU min(-1) to avoid saturation.
EPID images were acquired at the maximum frame-rate of 2.5 frame s(-1), and a
reduced dose-rate of 19 MU min(-1) to provide a similar dose per frame to the
APS. Signal-to-noise ratio (SNR) of the background signal and contrast-to-noise
ratio (CNR) of the marker signal relative to the background were evaluated for
both imagers at doses of 0.125 to 2 MU. RESULTS: Image quality and marker
visibility was found to be greater in the APS with SNR ~5 times greater than in
the EPID and CNR up to an order of magnitude greater for all four markers. To
investigate the ability to image and track moving markers the motion-platform was
moved to simulate a breathing cycle with period 6 s, amplitude 20 mm and maximum
speed 13.2 mm s(-1). At the minimum integration time of 50 ms a tracking
algorithm applied to the APS data found all four markers with a success rate of
>=92% and positional error <=90 MUm. At an integration time of 400 ms the
smallest marker became difficult to detect when moving. The detection of moving
markers using the a-Si EPID was difficult even at the maximum dose-rate of 592 MU
min(-1) due to the lower QE and longer integration time of 400 ms. CONCLUSIONS:
This work demonstrates that a fast read-out, high QE APS may be useful in the
tracking of moving fiducial markers during radiotherapy. Further study is
required to investigate the tracking of markers moving in 3D in a treatment beam
attenuated by moving patient anatomy. This will require a larger sensor with ROI
read-out to maintain speed and a manageable data-rate.
PMID- 22047381
TI - Auto-segmentation of normal and target structures in head and neck CT images: a
feature-driven model-based approach.
AB - PURPOSE: Intensity modulated radiation therapy (IMRT) allows greater control over
dose distribution, which leads to a decrease in radiation related toxicity. IMRT,
however, requires precise and accurate delineation of the organs at risk and
target volumes. Manual delineation is tedious and suffers from both interobserver
and intraobserver variability. State of the art auto-segmentation methods are
either atlas-based, model-based or hybrid however, robust fully automated
segmentation is often difficult due to the insufficient discriminative
information provided by standard medical imaging modalities for certain tissue
types. In this paper, the authors present a fully automated hybrid approach which
combines deformable registration with the model-based approach to accurately
segment normal and target tissues from head and neck CT images. METHODS: The
segmentation process starts by using an average atlas to reliably identify
salient landmarks in the patient image. The relationship between these landmarks
and the reference dataset serves to guide a deformable registration algorithm,
which allows for a close initialization of a set of organ-specific deformable
models in the patient image, ensuring their robust adaptation to the boundaries
of the structures. Finally, the models are automatically fine adjusted by our
boundary refinement approach which attempts to model the uncertainty in model
adaptation using a probabilistic mask. This uncertainty is subsequently resolved
by voxel classification based on local low-level organ-specific features.
RESULTS: To quantitatively evaluate the method, they auto-segment several organs
at risk and target tissues from 10 head and neck CT images. They compare the
segmentations to the manual delineations outlined by the expert. The evaluation
is carried out by estimating two common quantitative measures on 10 datasets:
volume overlap fraction or the Dice similarity coefficient (DSC), and a
geometrical metric, the median symmetric Hausdorff distance (HD), which is
evaluated slice-wise. They achieve an average overlap of 93% for the mandible,
91% for the brainstem, 83% for the parotids, 83% for the submandibular glands,
and 74% for the lymph node levels. CONCLUSIONS: Our automated segmentation
framework is able to segment anatomy in the head and neck region with high
accuracy within a clinically-acceptable segmentation time.
PMID- 22047382
TI - Radiochromic EBT2 film dosimetry for low-energy protontherapy.
AB - PURPOSE: In protontherapy, accessories are used in order to adapt the beam to the
surface and to the depth of the target. They are positioned close to the patient
in order to avoid perturbation effects related to proton scattering. The level of
contamination of the beam caused by these accessories may be assessed by
examining the dose maps in parallel planes to the beam incidence. The EBT2
radiochromic film is a suitable tool for this task, as it can be cut into small
pieces and immersed in water. Prior to use the EBT2 film for dose measurements,
its response when exposed to a proton beam must be analysed. METHODS: The
measurements were performed at the Centre Antoine Lacassagne, using the hospital
based MEDICYC isochronous cyclotron which provides 65 MeV protons. Monoenergetic
as well as polyenergetic beams were used. Small pieces of EBT2 films were
irradiated with proton beams in a small water phantom. Films were exposed at
various angles close to the beam incidence and received doses ranging from 0.25
to 500 Gy. The optical density (OD) was studied as a function of angle, dose and
linear energy transfer (LET). RESULTS: The effective atomic number of the active
layer of the film is close to that of water which prevents disturbances of the
measurement. However, the high density and the significant thickness of the Mylar
substrate surrounding the active layer affect the use of the film in a parallel
orientation to the beam. Therefore, the substrate layer may totally or partially
slow down the protons. The measurement is then no longer representative to what
happens in water. The measurement errors can be corrected by applying a tilt
angle of at least 5 degrees between the film and the beam. The dose analysis
reveals that the green channel is the most sensitive in the dose range from 1 to
100 Gy. The OD is accurately described by a Weibull function of the dose with
four free parameters. The Weibull function is valid for both monoenergetic and
polyenergetic beams if the LET is limited to values below 15 MeV g(- 1) cm(2).
When using a film orientation close to the beam incidence angle, increasing LET
values are encountered throughout the film axis gradually with the protons
slowing down in water. The EBT2 films show an underestimated response for higher
LET values. The comparison of data from the present study to data obtained by
other authors for EBT films allows modelling the underestimated response as a
function of the LET. The definition improvement of the link between OD and LET
requires to integrate more closely the beam energy characteristics. CONCLUSIONS:
The EBT2 film is a suitable dosimeter for analysing dose plans in planes nearly
parallel to the beam orientation by compensating the underestimated dose response
due to LET.
PMID- 22047383
TI - Automated 3-dimensional segmentation of pelvic lymph nodes in magnetic resonance
images.
AB - PURPOSE: Computer aided diagnosis (CAD) of lymph node metastases may help reduce
reading time and improve interpretation of the large amount of image data in a 3
D pelvic MRI exam. The purpose of this study was to develop an algorithm for
automated segmentation of pelvic lymph nodes from a single seed point, as part of
a CAD system for the classification of normal vs metastatic lymph nodes, and to
evaluate its performance compared to other algorithms. METHODS: The authors'
database consisted of pelvic MR images of 146 consecutive patients, acquired
between January 2008 and April 2010. Each dataset included four different MR
sequences, acquired after infusion of a lymph node specific contrast medium based
on ultrasmall superparamagnetic particles of iron oxide. All data sets were
analyzed by two expert readers who, reading in consensus, annotated and manually
segmented the lymph nodes. The authors compared four segmentation algorithms:
confidence connected region growing (CCRG), extended CCRG (ECC), graph cut
segmentation (GCS), and a segmentation method based on a parametric shape and
appearance model (PSAM). The methods were ranked based on spatial overlap with
the manual segmentations, and based on diagnostic accuracy in a CAD system, with
the experts' annotations as reference standard. RESULTS: A total of 2347 manually
annotated lymph nodes were included in the analysis, of which 566 contained a
metastasis. The mean spatial overlap (Dice similarity coefficient) was: 0.35
(CCRG), 0.57 (ECC), 0.44 (GCS), and 0.46 (PSAM). When combined with the
classification system, the area under the ROC curve was: 0.805 (CCRG), 0.890
(ECC), 0.807 (GCS), 0.891 (PSAM), and 0.935 (manual segmentation). CONCLUSIONS:
We identified two segmentation methods, ECC and PSAM, that achieve a high
diagnostic accuracy when used in conjunction with a CAD system for classification
of normal vs metastatic lymph nodes. The manual segmentations still achieve the
highest diagnostic accuracy.
PMID- 22047384
TI - Optimization of phosphor-based detector design for oblique x-ray incidence in
digital breast tomosynthesis.
AB - PURPOSE: In digital breast tomosynthesis (DBT), a volumetric reconstruction of
the breast is generated from a limited range of x-ray projections. One trade-off
of DBT is resolution loss in the projections due to non-normal (i.e., oblique) x
ray incidence. Although degradation in image quality due to oblique incidence has
been studied using empirical data and Monte Carlo simulations, a theoretical
treatment has been lacking. The purpose of this work is to extend Swank's
calculations of the transfer functions of turbid granular phosphors to oblique
incidence. The model is ultimately used as a tool for optimizing the design of
DBT detectors. METHODS: A quantum-limited system and 20 keV x-rays are
considered. Under these assumptions, the modulation transfer function (MTF) and
noise power spectra (NPS) are derived using the diffusion approximation to the
Boltzmann equation to model optical scatter within the phosphor. This approach is
applicable to a nonstructured scintillator such as gadolinium oxysulfide doped
with terbium (Gd(2)O(2)S:Tb), which is commonly used in breast imaging and which
can reasonably approximate other detector materials. The detective quantum
efficiency (DQE) is then determined from the Nishikawa formulation, where it is
written as the product of the x-ray quantum detection efficiency, the Swank
factor, and the Lubberts fraction. Transfer functions are calculated for both
front- and back-screen configurations, which differ by positioning the
photocathode at the exit or entrance point of the x-ray beam, respectively.
RESULTS: In the front-screen configuration, MTF and DQE are found to have
considerable angular dependence, while NPS is shown to vary minimally with
projection angle. As expected, the high frequency MTF and DQE are degraded
substantially at large angles. By contrast, all transfer functions for the back
screen configuration have the advantage of significantly less angular dependence.
Using these models, we investigated the possibility for optimizing the design of
DBT detectors. As an example optimization strategy, the phosphor thickness which
maximizes the DQE at a fixed frequency is analyzed. This work demonstrates that
the optimal phosphor thickness for the front-screen is angularly dependent,
shifting to lower thickness at higher angles. Conversely, the back-screen is not
optimized by a single thickness but instead attains reasonably high DQE values
over a large range of thicknesses. Although the back-screen configuration is not
suited for current detectors using a glass substrate, it may prove to be
preferred in future detectors using newly proposed plastic thin-film transistor
(TFT) substrates. CONCLUSIONS: Using the diffusion approximation to the Boltzmann
equation to model the spread of light in a scintillator, this paper develops an
analytical model of MTF, NPS, and DQE for a phosphor irradiated obliquely. The
model is set apart from other studies on oblique incidence in being derived from
first principles. This work has applications in the optimization of DBT detector
design.
PMID- 22047385
TI - An approach for online evaluations of dose consequences caused by small
rotational setup errors in intracranial stereotactic radiation therapy.
AB - PURPOSE: The purpose of this work is to investigate the impact of small
rotational errors on the magnitudes and distributions of spatial dose variations
for intracranial stereotactic radiotherapy (SRT) treatment setups, and to assess
the feasibility of using the original dose map overlaid with rotated contours
(ODMORC) method as a fast, online evaluation tool to estimate dose changes (using
DVHs) to clinical target volumes (CTVs) and organs-at-risks (OARs) caused by
small rotational setup errors. METHODS: Fifteen intracranial SRT cases treated
with either three-dimensional conformal radiation therapy (3DCRT) or intensity
modulated radiation therapy (IMRT) techniques were chosen for the study. Selected
cases have a variety of anatomical dimensions and pathologies. Angles of +/-3
degrees and +/-5 degrees in all directions were selected to simulate the
rotational errors. Dose variations in different regions of the brain, CTVs, and
OARs were evaluated to illustrate the various spatial effects of dose differences
before and after rotations. DVHs accounting for rotations that were recomputed by
the treatment planning system (TPS) and those generated by the ODMORC method were
compared. A framework of a fast algorithm for multicontour rotation implemented
by ODMORC is introduced as well. RESULTS: The average values of relative dose
variations between original dose and recomputed dose accounting for rotations
were greater than 4.0% and 10.0% in absolute mean and in standard deviation,
respectively, at the skull and adjacent regions for all cases. They were less
than 1.0% and 2.5% in absolute mean and in standard deviation, respectively, for
dose points 3 mm away from the skull. The results indicated that spatial dose to
any part of the brain organs or tumors separated from the skull or head surface
would be relatively stable before and after rotations. Statistical data of CTVs
and OARs indicate the lens and cochleas have the large dose variations before and
after rotations, whereas the remaining ROIs have insignificant dose differences.
DVH comparisons suggest that the ODMORC method is able to estimate the DVH of
CTVs fairly accurately (within 1.5% of relative dose differences for evaluation
volumes). The results also show that most of the OARs including the brain stem,
spinal cord, chiasm, hippocampuses, optic nerves, and retinas, which were
relatively distal from the skull and surface, had good agreement (within 2.0% of
relative dose differences for 0.1 cc of the volumes ) between the ODMORC method
and the recomputation, whereas OARs more proximate to the bone-tissue interface
or surface, such as the lenses and cochlea, had larger dose variations (greater
than 5.0%) for some cases due to the incapability of the ODMORC to account for
scatter contribution variations proximate to interfaces and intrinsic dose
calculation uncertainties for ROIs with small volumes. CONCLUSIONS: The ODMORC
method can be implemented as an online evaluation system for rotation-induced
dose changes of CTVs and most OARs and for other related dose consequence
analyses.
PMID- 22047386
TI - Assessment of three methods for detection of ultrasound artifacts.
AB - PURPOSE: The purpose of this work is to measure the performance (sensitivity and
specificity) of three different visually based methods of detecting ultrasound
artifacts using dynamic clips obtained with a liquid phantom. It is important to
detect the presence of these non uniformities as early as possible, so they can
be assessed, tracked, and addressed well before clinical image quality is
impacted. METHODS: A total of 28 transducers of varying models containing a
single artificial artifact created by stretching thin filaments across the
transducer face were prepared. A second set of 28 matching transducers contained
no artifacts. A 10 s clip was recorded of a dynamic speckle pattern from a custom
liquid phantom ("dynamic clip"). A single-frame image was obtained by computing
the median values at each pixel location over all frames of the clip ("median
image"). This single-frame median image was then subtracted from a baseline image
previously obtained with no induced artifact ("subtracted median"). All images
were evaluated by six observers. The mean sensitivity and specificity with 95%
exact binomial confidence intervals for the three artifact detection methods were
estimated. Evaluation time and observer confidence were recorded. RESULTS: Both
single-frame median and subtracted median images had a higher sensitivity than
the dynamic clip. Overall the subtracted median images had the highest
sensitivity of 97%, while maintaining a high specificity of 92%. Observers
identified artifacts in the shortest time and with the highest confidence with
this method. The subtracted median method removed the original structural
variations and non-uniformities, and reduced the likelihood of false-positives.
CONCLUSIONS: From the three methods assessed in this study, subtracted median
images allow detection of artifacts with very good sensitivity and specificity,
low image evaluation times, and a high degree of observer confidence, making
these ideal for routine QC. For acceptance testing, where there are no previous
baseline images available for subtraction, the use of median images is useful,
although comparison with median images from different transducers of the same
model and / or comparison of impressions from multiple observers should be made
to decrease the incidence of false-positive findings. If median and subtracted
median images are not available, direct inspection of the dynamic B-mode clips is
useful for acceptance testing and quality control, but with lower sensitivity and
somewhat longer evaluation time.
PMID- 22047387
TI - Megavoltage cone beam CT near surface dose measurements: potential implications
for breast radiotherapy.
AB - PURPOSE: Cone beam computed tomography (CBCT) is fast becoming standard on modern
linear accelerators. CBCT increases the dose to regions within and outside the
treatment field, potentially increasing secondary cancer induction and toxicity.
This study quantified megavoltage (MV) CBCT skin dose and compared it to skin
dose delivered during standard tangential breast radiotherapy. METHOD: Dosimetry
was performed both in- and out-of-field using thermoluminescent dosimeters (TLDs)
and a metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector
specifically designed for skin dosimetry; these were placed superficially on a
female anthropomorphic phantom. RESULTS: The skin dose from a single treatment
fraction ranged from 0.5 to 1.4 Gy on the ipsilateral breast, 0.031-0.18 Gy on
the contralateral breast, and 0-0.02 Gy in the head and pelvic region. An 8 MU MV
CBCT delivered a skin dose that ranged from 0.02 to 0.05 Gy in the chest region
and was less than 0.01 Gy in the head and pelvis regions. One MV CBCT per
fraction was found to increase the out-of-field skin dose from both the CBCT and
the treatment fields by approximately 20%. The imaging dose as a percentage of
treatment doses in the ipsilateral breast region was 3% for both dosimeters.
CONCLUSION: Imaging increases the skin dose to regions outside the treatment
field particularly regions immediately adjacent the target volume. This small
extra dose to the breasts should be considered when developing clinical protocols
and assessing dose for clinical trials.
PMID- 22047388
TI - Accuracy of Acuros XB and AAA dose calculation for small fields with reference to
RapidArc((r)) stereotactic treatments.
AB - PURPOSE: To assess the accuracy against measurements of two photon dose
calculation algorithms (Acuros XB and the Anisotropic Analytical algorithm AAA)
for small fields usable in stereotactic treatments with particular focus on
RapidArc((r)). METHODS: Acuros XB and AAA were configured for stereotactic use.
Baseline accuracy was assessed on small jaw-collimated open fields for different
values for the spot sizes parameter in the beam data: 0.0, 0.5, 1, and 2 mm. Data
were calculated with a grid of 1 * 1 mm(2). Investigated fields were: 3 * 3, 2 *
2, 1 * 1, and 0.8 * 0.8 cm(2) with a 6 MV photon beam generated from a
Clinac2100iX (Varian, Palo Alto, CA). Profiles, PDD, and output factors were
measured in water with a PTW diamond detector (detector size: 4 mm(2), thickness
0.4 mm) and compared to calculations. Four RapidArc test plans were optimized,
calculated and delivered with jaw settings J3 * 3, J2 * 2, and J1 * 1 cm(2), the
last was optimized twice to generate high (H) and low (L) modulation patterns.
Each plan consisted of one partial arc (gantry 110 degrees to 250 degrees ), and
collimator 45 degrees . Dose to isocenter was measured in a PTW Octavius phantom
and compared to calculations. 2D measurements were performed by means of portal
dosimetry with the GLAaS method developed at authors' institute. Analysis was
performed with gamma pass-fail test with 3% dose difference and 2 mm distance to
agreement thresholds. RESULTS: Open square fields: penumbrae from open field
profiles were in good agreement with diamond measurements for 1 mm spot size
setting for Acuros XB, and between 0.5 and 1 mm for AAA. Maximum MU difference
between calculations and measurements was 1.7% for Acuros XB (0.2% for fields
greater than 1 * 1 cm(2)) with 0.5 or 1 mm spot size. Agreement for AAA was
within 0.7% (2.8%) for 0.5 (1 mm) spot size. RapidArc plans: doses were evaluated
in a 4 mm diameter structure at isocenter and computed values differed from
measurements by 0.0, -0.2, 5.5, and -3.4% for Acuros XB calculations (1 mm spot
size), and of -0.1, 0.3, 6.7, and -1.2% for AAA, respectively for J3 * 3, J2 * 2,
J1 * 1H, J1 * 1L RapidArc plans. Gamma Agreement Index from 2D dose analysis was
higher than 95% for J3 * 3 and J2 * 2 plans, being around 80% for J1 * 1 maps.
Sensitivity with respect to the dosimetric leaf gap and transmission factor MLC
parameters was evaluated in the four RapidArc plans, showing the need to properly
set the dosimetric leaf gap for accurate calculations. CONCLUSIONS: Acuros XB and
AAA showed acceptable characteristics for stereotactic small fields if adequate
tuning of configuration parameters is performed. Dose calculated for RapidArc
stereotactic plans showed an acceptable agreement against point and 2D
measurements. Both algorithms can therefore be considered safely applicable to
stereotactic treatments.
PMID- 22047389
TI - A robust and efficient approach to detect 3D rectal tubes from CT colonography.
AB - PURPOSE: The rectal tube (RT) is a common source of false positives (FPs) in
computer-aided detection (CAD) systems for CT colonography. A robust and
efficient detection of RT can improve CAD performance by eliminating such
"obvious" FPs and increase radiologists' confidence in CAD. METHODS: In this
paper, we present a novel and robust bottom-up approach to detect the RT.
Probabilistic models, trained using kernel density estimation on simple low-level
features, are employed to rank and select the most likely RT tube candidate on
each axial slice. Then, a shape model, robustly estimated using random sample
consensus (RANSAC), infers the global RT path from the selected local detections.
Subimages around the RT path are projected into a subspace formed from training
subimages of the RT. A quadratic discriminant analysis (QDA) provides a
classification of a subimage as RT or non-RT based on the projection. Finally, a
bottom-top clustering method is proposed to merge the classification predictions
together to locate the tip position of the RT. RESULTS: Our method is validated
using a diverse database, including data from five hospitals. On a testing data
with 21 patients (42 volumes), 99.5% of annotated RT paths have been successfully
detected. Evaluated with CAD, 98.4% of FPs caused by the RT have been detected
and removed without any loss of sensitivity. CONCLUSIONS: The proposed method
demonstrates a high detection rate of the RT path, and when tested in a CAD
system, reduces FPs caused by the RT without the loss of sensitivity.
PMID- 22047390
TI - Comparison of secondary neutron dose in proton therapy resulting from the use of
a tungsten alloy MLC or a brass collimator system.
AB - PURPOSE: To apply the dual ionization chamber method for mixed radiation fields
to an accurate comparison of the secondary neutron dose arising from the use of a
tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system
for defining the shape of a therapeutic proton field. METHODS: Hydrogenous and
nonhydrogenous ionization chambers were constructed with large volumes to enable
measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using
the dual ionization chamber method for mixed-field dosimetry. Neutron dose
measurements were made with a nominal 230 MeV proton beam incident on a closed
tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated
against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and
Monte Carlo simulations were performed to account for variations in ionization
chamber response due to differences in secondary neutron energy spectra. RESULTS:
The neutron and combined proton plus gamma-ray absorbed doses are shown to be
nearly equivalent downstream from either a closed tungsten alloy MLC or a solid
brass block. At 10 cm downstream from the distal edge of the collimating material
the neutron dose from the closed MLC was (5.3 +/- 0.4) * 10(- 5) Gy/Gy. The
neutron dose with brass was (6.4 +/- 0.7) * 10(- 5) Gy/Gy. Further from the
secondary neutron source, at 50 cm, the neutron doses remain close for both the
MLC and brass block at (6.9 +/- 0.6) * 10(- 6) Gy/Gy and (6.3 +/- 0.7) * 10(- 6)
Gy/Gy, respectively. CONCLUSIONS: The dual ionization chamber method is suitable
for measuring secondary neutron doses resulting from proton irradiation. The
results of measurements downstream from a closed tungsten alloy MLC and a brass
block indicate that, even in an overly pessimistic worst-case scenario, secondary
neutron production in a tungsten alloy MLC leads to absorbed doses that are
nearly equivalent to those seen from brass collimators. Therefore, the choice of
tungsten alloy in constructing the leaves of a proton MLC is appropriate, and
does not lead to a substantial increase in the secondary neutron dose to the
patient compared to that generated in a brass collimator.
PMID- 22047391
TI - Direct dose to water dosimetry for pretreatment IMRT verification using a
modified EPID.
AB - PURPOSE: Electronic portal imaging devices (EPIDs) are high resolution systems
that produce electronic dose maps with minimal time required for equipment setup,
and therefore potentially present a time-saving alternative for intensity
modulated radiation therapy (IMRT) pretreatment verification. A modified
commercial EPID was investigated operated with an opaque sheet blocking the
optical signal produced in the phosphor layer as a precursor to a switched mode
dual dosimetry-imaging EPID system. The purpose of this study was to investigate
the feasibility of using this system for direct dose to water dosimetry for
pretreatment IMRT verification. METHODS: A Varian amorphous silicon EPID was
modified by placing an opaque sheet between the Gd(2)S(2)O:Tb phosphor layer and
the photodiode array to block the optical photons. The EPID was thus converted to
a direct-detecting system (dEPID), in which the high energy radiation deposits
energy directly in the photodiode array. The copper build-up was replaced with
d(max) solid water. Sixty-one IMRT beams of varying complexity were delivered to
the EPID, to EDR2 dosimetric film and to a 2D ion chamber array (MapCheck). EPID
data was compared to film and MapCheck data using gamma analysis with 3%, 3mm
pass criteria. RESULTS: The fraction of points that passed the gamma test was on
average 98.1% and 98.6%, for the EPID versus film and EPID versus MapCheck
comparisons, respectively. In the case of comparison with film, the majority of
observed discrepancies were associated with problems related to film sensitivity
or processing. CONCLUSIONS: The very close agreement between EPID and both film
and MapCheck data demonstrates that the modified EPID is suitable for direct dose
to water measurement for pretreatment IMRT verification. These results suggest a
reconfigured EPID could be an efficient and accurate dosimeter. Alternatively,
optical switching methods could be developed to produce a dual-mode EPID with
both dosimetry and imaging capabilities.
PMID- 22047392
TI - Comparison and assessment of semi-automatic image segmentation in computed
tomography scans for image-guided kidney surgery.
AB - PURPOSE: Image segmentation is integral to implementing intraoperative guidance
for kidney tumor resection. Results seen in computed tomography (CT) data are
affected by target organ physiology as well as by the segmentation algorithm
used. This work studies variables involved in using level set methods found in
the Insight Toolkit to segment kidneys from CT scans and applies the results to
an image guidance setting. METHODS: A composite algorithm drawing on the
strengths of multiple level set approaches was built using the Insight Toolkit.
This algorithm requires image contrast state and seed points to be identified as
input, and functions independently thereafter, selecting and altering method and
variable choice as needed. RESULTS: Semi-automatic results were compared to
expert hand segmentation results directly and by the use of the resultant
surfaces for registration of intraoperative data. Direct comparison using the
Dice metric showed average agreement of 0.93 between semi-automatic and hand
segmentation results. Use of the segmented surfaces in closest point registration
of intraoperative laser range scan data yielded average closest point distances
of approximately 1 mm. Application of both inverse registration transforms from
the previous step to all hand segmented image space points revealed that the
distance variability introduced by registering to the semi-automatically
segmented surface versus the hand segmented surface was typically less than 3 mm
both near the tumor target and at distal points, including subsurface points.
CONCLUSIONS: Use of the algorithm shortened user interaction time and provided
results which were comparable to the gold standard of hand segmentation. Further,
the use of the algorithm's resultant surfaces in image registration provided
comparable transformations to surfaces produced by hand segmentation. These data
support the applicability and utility of such an algorithm as part of an image
guidance workflow.
PMID- 22047393
TI - Fluorescence diffuse optical tomography using the split Bregman method.
AB - PURPOSE: Standard image reconstruction methods for fluorescence Diffuse Optical
Tomography (fDOT) generally make use of L2-regularization. A better choice is to
replace the L2 by a total variation functional that effectively removes noise
while preserving edges. Among the wide range of approaches available, the
recently appeared Split Bregman method has been shown to be optimal and
efficient. Furthermore, additional constraints can be easily included. We propose
the use of the Split Bregman method to solve the image reconstruction problem for
fDOT with a nonnegativity constraint that imposes the reconstructed concentration
of fluorophore to be positive. METHODS: The proposed method is tested with
simulated and experimental data, and results are compared with those yielded by
an equivalent unconstrained optimization approach based on Gauss-Newton (GN)
method, in which the negative part of the solution is projected to zero after
each iteration. In addition, the method dependence on the parameters that weigh
data fidelity and nonnegativity constraints is analyzed. RESULTS: Split Bregman
yielded a reduction of the solution error norm and a better full width at tenth
maximum for simulated data, and higher signal-to-noise ratio for experimental
data. It is also shown that it led to an optimum solution independently of the
data fidelity parameter, as long as the number of iterations is properly
selected, and that there is a linear relation between the number of iterations
and the inverse of the data fidelity parameter. CONCLUSIONS: Split Bregman allows
the addition of a nonnegativity constraint leading to improve image quality.
PMID- 22047394
TI - Automated intraoperative calibration for prostate cancer brachytherapy.
AB - PURPOSE: Prostate cancer brachytherapy relies on an accurate spatial registration
between the implant needles and the TRUS image, called "calibration". The authors
propose a new device and a fast, automatic method to calibrate the brachytherapy
system in the operating room, with instant error feedback. METHODS: A device was
CAD-designed and precision-engineered, which mechanically couples a calibration
phantom with an exact replica of the standard brachytherapy template. From real
time TRUS images acquired from the calibration device and processed by the
calibration system, the coordinate transformation between the brachytherapy
template and the TRUS images was computed automatically. The system instantly
generated a report of the target reconstruction accuracy based on the current
calibration outcome. RESULTS: Four types of validation tests were conducted.
First, 50 independent, real-time calibration trials yielded an average of 0.57 +/
0.13 mm line reconstruction error (LRE) relative to ground truth. Second, the
averaged LRE was 0.37 +/- 0.25 mm relative to ground truth in tests with six
different commercial TRUS scanners operating at similar imaging settings.
Furthermore, testing with five different commercial stepper systems yielded an
average of 0.29 +/- 0.16 mm LRE relative to ground truth. Finally, the system
achieved an average of 0.56 +/- 0.27 mm target registration error (TRE) relative
to ground truth in needle insertion tests through the template in a water tank.
CONCLUSIONS: The proposed automatic, intraoperative calibration system for
prostate cancer brachytherapy has achieved high accuracy, precision, and
robustness.
PMID- 22047395
TI - Flow characteristics in a canine aneurysm model: a comparison of 4D accelerated
phase-contrast MR measurements and computational fluid dynamics simulations.
AB - PURPOSE: Our purpose was to compare quantitatively velocity fields in and around
experimental canine aneurysms as measured using an accelerated 4D PC-MR
angiography (MRA) method and calculated based on animal-specific CFD simulations.
METHODS: Two animals with a surgically created bifurcation aneurysm were imaged
using an accelerated 4D PC-MRA method. Meshes were created based on the
geometries obtained from the PC-MRA and simulations using "subject-specific"
pulsatile velocity waveforms and geometries were then solved using a commercial
CFD solver. Qualitative visual assessments and quantitative comparisons of the
time-resolved velocity fields obtained from the PC-MRA measurements and the CFD
simulations were performed using a defined similarity metric combining both
angular and magnitude differences of vector fields. RESULTS: PC-MRA and image
based CFD not only yielded visually consistent representations of 3D streamlines
in and around both aneurysms, but also showed good agreement with regard to the
spatial velocity distributions. The estimated similarity between time-resolved
velocity fields from both techniques was reasonably high (mean value >0.60; one
being the highest and zero being the lowest). Relative differences in inflow and
outflow zones among selected planes were also reasonable (on the order of 10%
20%). The correlation between CFD-calculated and PC-MRA-measured time-averaged
wall shear stresses was low (0.22 and 0.31, p < 0.001). CONCLUSIONS: In two
experimental canine aneurysms, PC-MRA and image-based CFD showed favorable
agreement in intra-aneurismal velocity fields. Combining these two complementary
techniques likely will further improve the ability to characterize and interpret
the complex flow that occurs in human intracranial aneurysms.
PMID- 22047396
TI - Automatic 3D registration of dynamic stress and rest (82)Rb and flurpiridaz F 18
myocardial perfusion PET data for patient motion detection and correction.
AB - PURPOSE: The authors aimed to develop an image-based registration scheme to
detect and correct patient motion in stress and rest cardiac positron emission
tomography (PET)/CT images. The patient motion correction was of primary interest
and the effects of patient motion with the use of flurpiridaz F 18 and (82)Rb
were demonstrated. METHODS: The authors evaluated stress/rest PET myocardial
perfusion imaging datasets in 30 patients (60 datasets in total, 21 male and 9
female) using a new perfusion agent (flurpiridaz F 18) (n = 16) and (82)Rb (n =
14), acquired on a Siemens Biograph-64 scanner in list mode. Stress and rest
images were reconstructed into 4 ((82)Rb) or 10 (flurpiridaz F 18) dynamic frames
(60 s each) using standard reconstruction (2D attenuation weighted ordered
subsets expectation maximization). Patient motion correction was achieved by an
image-based registration scheme optimizing a cost function using modified
normalized cross-correlation that combined global and local features. For
comparison, visual scoring of motion was performed on the scale of 0 to 2 (no
motion, moderate motion, and large motion) by two experienced observers. RESULTS:
The proposed registration technique had a 93% success rate in removing left
ventricular motion, as visually assessed. The maximum detected motion extent for
stress and rest were 5.2 mm and 4.9 mm for flurpiridaz F 18 perfusion and 3.0 mm
and 4.3 mm for (82)Rb perfusion studies, respectively. Motion extent (maximum
frame-to-frame displacement) obtained for stress and rest were (2.2 +/- 1.1, 1.4
+/- 0.7, 1.9 +/- 1.3) mm and (2.0 +/- 1.1, 1.2 +/-0 .9, 1.9 +/- 0.9) mm for
flurpiridaz F 18 perfusion studies and (1.9 +/- 0.7, 0.7 +/- 0.6, 1.3 +/- 0.6) mm
and (2.0 +/- 0.9, 0.6 +/- 0.4, 1.2 +/- 1.2) mm for (82)Rb perfusion studies,
respectively. A visually detectable patient motion threshold was established to
be >=2.2 mm, corresponding to visual user scores of 1 and 2. After motion
correction, the average increases in contrast-to-noise ratio (CNR) from all
frames for larger than the motion threshold were 16.2% in stress flurpiridaz F 18
and 12.2% in rest flurpiridaz F 18 studies. The average increases in CNR were
4.6% in stress (82)Rb studies and 4.3% in rest (82)Rb studies. CONCLUSIONS: Fully
automatic motion correction of dynamic PET frames can be performed accurately,
potentially allowing improved image quantification of cardiac PET data.
PMID- 22047397
TI - Suitability of miniature inductively coupled RF coils as MR-visible markers for
clinical purposes.
AB - PURPOSE: MR-visible markers have already been used for various purposes such as
image registration, motion detection, and device tracking. Inductively coupled RF
(ICRF) coils, in particular, provide a high contrast and do not require
connecting wires to the scanner, which makes their application highly flexible
and safe. This work aims to thoroughly characterize the MR signals of such ICRF
markers under various conditions with a special emphasis on fully automatic
detection. METHODS: The small markers consisted of a solenoid coil that was wound
around a glass tube containing the MR signal source and tuned to the resonance
frequency of a 1.5 T MRI. Marker imaging was performed with a spoiled gradient
echo sequence (FLASH) and a balanced steady-state free precession (SSFP) sequence
(TrueFISP) in three standard projections. The signal intensities of the markers
were recorded for both pulse sequences, three source materials (tap water,
distilled water, and contrast agent solution), different flip angles and coil
alignments with respect to the B(0) direction as well as for different marker
positions in the entire imaging volume (field of view, FOV). Heating of the ICRF
coils was measured during 10-min RF expositions to three conventional pulse
sequences. Clinical utility of the markers was assessed from their performance in
computer-aided detection and in defining double oblique scan planes. RESULTS: For
almost the entire FOV (+/-215 mm) and an estimated 82% of all possible RF coil
alignments with respect to B(0), the ICRF markers generated clearly visible MR
signals and could be reliably localized over a large range of flip angles, in
particular with the TrueFISP sequence (0.3 degrees -4.0 degrees ). Generally,
TrueFISP provided a higher marker contrast than FLASH. RF exposition caused a
moderate heating (<=5 degrees C) of the ICRF coils only. CONCLUSIONS: Small ICRF
coils, imaged at low flip angles with a balanced SSFP sequence showed an
excellent performance under a variety of experimental conditions and therefore
make for a reliable, compact, flexible, and relatively safe marker for clinical
use.
PMID- 22047398
TI - Development of a human-tissue-like phantom for 3.0-T MRI.
AB - PURPOSE: A 3.0-T MRI phantom having human-tissue-equivalent relaxation times was
developed. METHODS: The ingredients of the phantom are carrageenan (for
gelatinization), GdCl(3) (as a T(1)-relaxation modifier), agarose (as a T(2)
relaxation modifier), and NaN(3) (as an antiseptic agent). Numerous samples with
varying concentrations of GdCl(3) and agarose were prepared, and T(1) and T(2)
were measured using 3.0-T MRI. RESULTS: Relaxation times of the phantom samples
ranged from 395 to 2601 ms for T(1) values and 29 to 334 ms for T(2) values.
Based on the measured results, empirical formulae were devised to express the
relationships between the concentrations of relaxation modifiers and relaxation
times. CONCLUSIONS: Adjustment of GdCl(3) and agarose concentrations allows
arbitrary setting of relaxation times, and the creation of a phantom that can
mimic relaxation times of human-tissue. Carrageenan is considered the most
suitable as a gelling agent for an MRI phantom, as it permits the relatively easy
and inexpensive production of a large phantom such as for the human torso, and
which can be easily shaped with a knife.
PMID- 22047399
TI - A few words on evidence based medicine.
PMID- 22047400
TI - Multileaf collimators, air gap, lateral penumbra, and range compensation in
proton radiotherapy.
PMID- 22047401
TI - Direct mechanical measurements reveal the material properties of three
dimensional DNA origami.
AB - The application of three-dimensional DNA origami objects as rigid mechanical
mediators or force sensing elements requires detailed knowledge about their
complex mechanical properties. Using magnetic tweezers, we directly measure the
bending and torsional rigidities of four- and six-helix bundles assembled by this
technique. Compared to duplex DNA, we find the bending rigidities to be greatly
increased while the torsional rigidities are only moderately augmented. We
present a mechanical model explicitly including the crossovers between the
individual helices in the origami structure that reproduces the experimentally
observed behavior. Our results provide an important basis for the future
application of 3D DNA origami in nanomechanics.
PMID- 22047402
TI - RNA-Seq improves annotation of protein-coding genes in the cucumber genome.
AB - BACKGROUND: As more and more genomes are sequenced, genome annotation becomes
increasingly important in bridging the gap between sequence and biology. Gene
prediction, which is at the center of genome annotation, usually integrates
various resources to compute consensus gene structures. However, many newly
sequenced genomes have limited resources for gene predictions. In an effort to
create high-quality gene models of the cucumber genome (Cucumis sativus var.
sativus), based on the EVidenceModeler gene prediction pipeline, we incorporated
the massively parallel complementary DNA sequencing (RNA-Seq) reads of 10
cucumber tissues into EVidenceModeler. We applied the new pipeline to the
reassembled cucumber genome and included a comparison between our predicted
protein-coding gene sets and a published set. RESULTS: The reassembled cucumber
genome, annotated with RNA-Seq reads from 10 tissues, has 23, 248 identified
protein-coding genes. Compared with the published prediction in 2009,
approximately 8, 700 genes reveal structural modifications and 5, 285 genes only
appear in the reassembled cucumber genome. All the related results, including
genome sequence and annotations, are available at
http://cmb.bnu.edu.cn/Cucumis_sativus_v20/. CONCLUSIONS: We conclude that RNA-Seq
greatly improves the accuracy of prediction of protein-coding genes in the
reassembled cucumber genome. The comparison between the two gene sets also
suggests that it is feasible to use RNA-Seq reads to annotate newly sequenced or
less-studied genomes.
PMID- 22047403
TI - Laparoscopic cholecystectomy without handling the cystic artery: a new approach
to minimize complications.
AB - INTRODUCTION: Although laparoscopy has now become the procedure of choice for
removal of gallbladder, complications especially injury to cystic artery and
ducts are thought to be higher. We describe a technique that avoids handling and
injury of cystic artery and resultant duct injuries. The video length is 2
minutes 13 seconds. MATERIALS AND METHODS: From October 7, 2005, to December 31,
2010, 17 patients were successfully operated by the cystic artery sparing
technique. In this technique, dissection begins distal to cystic lymph node on
the gallbladder wall using hook cautery, thereby clears the Calot's triangle
without even touching the cystic artery. This maneuver eliminates the risk of
injuring thus causing bleeding and any subsequent complications. Age, sex, and
operative outcomes including follow-ups were evaluated. RESULTS: Age of the
patients ranged from 3.4 years to 16 years with an average of 10.12 years. Males
were predominant (10:7). Average operative time was 40 minutes. There were no
intraoperative or immediate postoperative complications. Patients were allowed
feeding 4-6 hours after operation and discharged the following morning. Patients
were asked to come for follow-up at 1 week, 1 month, 3 months, 6 months, and 1
year and thereafter yearly. Follow-up period ranged from 6 months to 5 years.
There were no operation-related complications other than minor abdominal pain in
3 patients and port-site pain in 2 patients which resolved on conservative
treatments. CONCLUSION: During laparoscopic cholecystectomy, if handling of the
main cystic artery is avoided then complications of hemorrhage and bile duct
injuries can be minimized.
PMID- 22047404
TI - Laparoscopic gastric pull-up and thoracoscopic esophago-esophagostomy combined
with intrathoracic fundoplication for long-gap pure esophageal atresia.
AB - The management of long-gap pure esophageal atresia (LGEA) remains controversial.
An 8-month-old girl with LGEA underwent a laparoscopic and thoracoscopic gastric
pull-up and esophago-esophagostomy in the right thorax combined with
intrathoracic fundoplication. She was positioned supine, and three 5-mm ports
were placed in the standard locations for laparoscopic Nissen fundoplication. The
gastrostomy was taken down and an additional 5-mm port was inserted at the
gastrostomy site. Laparoscopic gastric mobilization was performed; the short
gastric and left gastric vessels were divided using harmonic shears, and the
whole stomach and distal esophageal stump maintained their vascular supply via
the right gastric and gastroepiploic arteries. The hiatus was enlarged by radial
incisions at both cruras, and the mobilized whole stomach and distal esophageal
stump were pushed up into the right thorax through the hiatus. The patient was
placed in a modified prone position and three 5-mm ports were inserted into the
right thorax. Via thoracoscopy, the upper esophageal pouch was dissected bluntly,
and an esophago-esophagostomy was performed using interrupted 4-0 absorbable
sutures and was wrapped by a 360-degree gastric fundoplication. The patient was
positioned supine again, and a Heinecke-Mikulicz pyloroplasty and gastropexy were
also performed laparoscopically. The patient has mild respiratory distress that
requires bronchodilators; however, she is eating baby food well without vomiting.
Postoperative intrathoracic gastrofiberscopy showed a well-functioning antireflux
valve, and her parents are also satisfied with the cosmetic appearance of the
seven small wounds. Our new procedure is feasible and is an excellent option in
selected patients with LGEA.
PMID- 22047405
TI - Sampling medium side resistance to uptake of semivolatile organic compounds in
passive air samplers.
AB - Current theory of the uptake of semivolatile organic compounds in passive air
samplers (PAS) assumes uniform chemical distribution and no kinetic resistance
within the passive sampling media (PSM) such as polystyrene-divinylbenzene resin
(XAD) and polyurethane foam (PUF). However, these assumptions have not been
tested experimentally and are challenged by some recently reported observations.
To test the assumptions, we performed kinetic uptake experiments indoors using
cylindrical PSM that had been concentrically segmented into three layers. Both
XAD and PUF were positioned in the same type of sampler housing to eliminate the
variation caused by the different housing designs, which enabled us to quantify
differences in uptake caused by the properties of the PSM. Duplicated XAD (PUF)
samples were retrieved after being deployed for 0, 1 (0.5), 2 (1), 4 (2), 8 (4),
12 (8), and 24 (12) weeks. Upon retrieval, the PSM layers were separated and
analyzed individually for PCBs. Passive sampling rates (R) were lower for heavier
PCB homologues. Within a homologue group, R for XAD was higher than that for PUF,
from which we infer that the design of the "cylindrical can" housing typically
used for XAD PAS lowers the R compared to the "double bowl" shelter commonly used
for PUF-disk PAS. Outer layers of the PSM sequestered much higher levels of PCBs
than inner layers, indicative of a kinetic resistance to chemical transfer within
the PSM. The effective diffusivities for chemical transfer within PSM were
derived and were found negatively correlated with the partition coefficients
between the PSM and air. Based on the results, we conclude that the PSM-side
kinetic resistance should be considered when investigating factors influencing R
and when deriving R based on the loss of depuration compounds.
PMID- 22047407
TI - Management of congestive heart failure in dogs.
PMID- 22047406
TI - YY1 overexpression is associated with poor prognosis and metastasis-free survival
in patients suffering osteosarcoma.
AB - BACKGROUND: The polycomb transcription factor Yin Yang 1 (YY1) overexpression can
be causally implicated in experimental tumor growth and metastasization. To date,
there is no clinical evidence of YY1 involvement in outcome of patients with
osteosarcoma. Prognosis of osteosarcoma is still severe and only few patients
survive beyond five years. We performed a prospective immunohistochemistry
analysis to correlate YY1 immunostaining with metastatic development and survival
in a selected homogeneous group of patients with osteosarcoma. METHODS: We
studied 41 patients suffering from osteosarcoma (stage II-IVa). Multivariate
analysis was performed using Cox proportional hazard regression to evaluate the
correlation between YY1 expression and both metastasis development and mortality.
RESULTS: YY1 protein is not usually present in normal bone; in contrast, a high
number of patients (61%) showed a high score of YY1 positive cells (51-100%) and
39% had a low score (10-50% positive cells). No statistical difference was found
in histology, anatomic sites, or response to chemotherapy between the two degrees
of YY1 expression. Cox regression analysis demonstrated that the highest score of
YY1 expression was predictive of both low metastasis-free survival (HR = 4.690,
95%CI = 1.079-20.396; p = 0.039) and poor overall survival (HR = 8.353, 95%CI =
1.863-37.451 p = 0.006) regardless of the effects of covariates such as age,
gender, histology and chemonecrosis. CONCLUSION: Overexpression of YY1 in primary
site of osteosarcoma is associated with the occurrence of metastasis and poor
clinical outcome.
PMID- 22047408
TI - Feline restrictive cardiomyopathy.
PMID- 22047409
TI - The neurological examination.
PMID- 22047410
TI - Chronic nasal and oral disease in cats.
PMID- 22047411
TI - Feline oncology.
PMID- 22047412
TI - Cutaneous manifestations and markers of systemic disease.
PMID- 22047413
TI - Problem-solving dermatology: Case presentations.
PMID- 22047414
TI - Plasma angiotensin II concentrations and the effect of treatment with enalapril
in dogs with proteinuria due to renal disease.
PMID- 22047416
TI - Stifle surgery.
PMID- 22047415
TI - Hepatic arteriovenous fistulas and hepatic portal vein hypoplasia in a labrador
retriever.
PMID- 22047417
TI - Wound management principles and techniques.
PMID- 22047418
TI - Skin flap and skin grafting techinques in small animal surgery.
PMID- 22047419
TI - New techniques in small animal reconstructive surgery.
PMID- 22047420
TI - Surgical diseases of the perineum.
PMID- 22047421
TI - Clinical efficacy of vedaprofen in dogs suffering from disorders of the
misculoskeletal system.
PMID- 22047422
TI - Voiding urohydropropulsion: An alternative to cystotomy.
PMID- 22047423
TI - Diagnostic pitfalls: Misdiagnosing causes of urinary tract signs.
PMID- 22047424
TI - Reproductive problems in the bitch and the queen.
PMID- 22047425
TI - Nonsurgical retrieval of uroliths for mineral analysis.
PMID- 22047426
TI - Progestins and mammary growth hormone production in the dog.
PMID- 22047428
TI - Surgery and prognosis in dogs with ectopic ureters.
PMID- 22047427
TI - Treatment of urinary incontinence in the bitch: A pilot field study with
incurin(r)
PMID- 22047429
TI - Cat scratch disease: Studies on diagnosis and identification of reservoirs and
vectors.
PMID- 22047430
TI - Canine and feline superficial fungal skin infections.
PMID- 22047432
TI - Some other virus infections of cats.
PMID- 22047431
TI - The role of bordetella bronchiseptica in feline respiratory disease.
PMID- 22047433
TI - Prevalence of antibodies against bordetella bronchiseptica in cats with a history
of respiratory disease.
PMID- 22047434
TI - Comparative study with 5 different distemper vaccines.
PMID- 22047436
TI - Surveys on the prevalence of intestinal nematodes in dogs and cats in the
Netherlands.
PMID- 22047435
TI - Update on the sensitivity of recent European canine and feline pathogens to
Marbofloxacin.
PMID- 22047437
TI - Radiology and ultrasonography of the urinary tract.
PMID- 22047438
TI - Basic principles for interpretation of cytologic preparations.
PMID- 22047440
TI - Pituitary-adrenocortical function and glucocorticoid administration in pigeons.
PMID- 22047439
TI - Evaluation of environmental enrichment for laboratory mice.
PMID- 22047441
TI - Proventriculotomy in 21 ostriches, a retrospective study.
PMID- 22047442
TI - The approach to orbital disease in the dog and cat.
PMID- 22047443
TI - Feline herpetic ocular disease.
PMID- 22047444
TI - Persistent hyperplastic tunica vasculosa lentis and persistent hyaloid artery in
a 2-year-old basset hound.
PMID- 22047446
TI - Psychosocial stressors and depression at a Swedish primary health care centre. A
gender perspective study.
AB - BACKGROUND: Psychosocial stress may account for the higher prevalence of
depression in women and in individuals with a low educational background. The aim
of this study was to analyse the association between depression and socio
demographic data, psychosocial stressors and lifestyle circumstances from a
gender perspective in a relatively affluent primary care setting. METHODS:
Patients, aged 18- 75 years, visiting a drop-in clinic at a primary care health
centre were screened with Beck's Depression Inventory (BDI). The physicians used
also targeted screening with BDI. A questionnaire on socio-demographic data,
psychosocial stressors and use of alcohol and tobacco was distributed. Among
patients, who scored BDI >= 10, DSM-IV-criteria were used to diagnose depression.
Of the 404 participants, 48 men and 76 women were diagnosed with depression. The
reference group consisted of patients with BDI score <10, 187 men and 93 women.
Age-adjusted odds ratios (ORs) with 95% confidence intervals (CI) as being
depressed were calculated for the psychosocial stressors and lifestyle
circumstances, separately for men and women. Multiple logistic regression
analyses were used to determine the age-adjusted main effect models for men and
women. RESULTS: The same three psychosocial stressors: feeling very stressed,
perceived poor physical health and being dissatisfied with one's family situation
were associated with depression equally in men and women. The negative predictive
values of the main effect models in men and women were 90.7% and 76.5%,
respectively. Being dissatisfied with one's work situation had high ORs in both
men and women. Unemployment and smoking were associated with depression in men
only. CONCLUSIONS: Three questions, frequently asked by physicians, which involve
patient's family and working situation as well as perceived stress and physical
health, could be used as depression indicators in early detection of depression
in men and women in primary health care.
PMID- 22047447
TI - Nonvisual arrestins function as simple scaffolds assembling the MKK4-JNK3alpha2
signaling complex.
AB - Arrestins make up a small family of proteins with four mammalian members that
play key roles in the regulation of multiple G protein-coupled receptor-dependent
and -independent signaling pathways. Although arrestins were reported to serve as
scaffolds for MAP kinase cascades, promoting the activation of JNK3, ERK1/2, and
p38, the molecular mechanisms involved were not elucidated, and even the direct
binding of arrestins with MAP kinases was never demonstrated. Here, using
purified proteins, we show that both nonvisual arrestins directly bind JNK3alpha2
and its upstream activator MKK4, and that the affinity of arrestin-3 for these
kinases is higher than that of arrestin-2. Reconstitution of the MKK4-JNK3alpha2
signaling module from pure proteins in the presence of different arrestin-3
concentrations showed that arrestin-3 acts as a "true" scaffold, facilitating
JNK3alpha2 phosphorylation by bringing the two kinases together. Both the level
of JNK3alpha2 phosphorylation by MKK4 and JNK3alpha2 activity toward its
substrate ATF2 increase at low and then decrease at high arrestin-3 levels,
yielding a bell-shaped concentration dependence expected with true scaffolds that
do not activate the upstream kinase or its substrate. Thus, direct binding of
both kinases and true scaffolding is the molecular mechanism of action of
arrestin-3 on the MKK4-JNK3alpha2 signaling module.
PMID- 22047448
TI - Salmonella Typhimurium-specific bacteriophage PhiSH19 and the origins of species
specificity in the Vi01-like phage family.
AB - BACKGROUND: Whole genome sequencing of bacteriophages suitable for biocontrol of
pathogens in food products is a pre-requisite to any phage-based intervention
procedure. Trials involving the biosanitization of Salmonella Typhimurium in the
pig production environment identified one such candidate, PhiSH19. RESULTS: This
phage was sequenced and analysis of its 157,785 bp circular dsDNA genome revealed
a number of interesting features. PhiSH19 constitutes another member of the
recently-proposed Myoviridae Vi01-like family of phages, containing S. Typhi
specific Vi01 and Shigella-specific SboM-AG3. At the nucleotide level PhiSH19 is
highly similar to phage Vi01 (80-98% pairwise identity over the length of the
genome), with the major differences lying in the region associated with host
range determination. Analyses of the proteins encoded within this region by
PhiSH19 revealed a cluster of three putative tail spikes. Of the three tail
spikes, two have protein domains associated with the pectate lyase family of
proteins (Tsp2) and P22 tail spike family (Tsp3) with the prospect that these
enable Salmonella O antigen degradation. Tail spike proteins of Vi01 and SboM-AG3
are predicted to contain conserved right-handed parallel beta-helical structures
but the internal protein domains are varied allowing different host
specificities. CONCLUSIONS: The addition or exchange of tail spike protein
modules is a major contributor to host range determination in the Vi01-like phage
family.
PMID- 22047449
TI - Evaluation of microgap size and microbial leakage in the connection area of 4
abutments with Straumann (ITI) implant.
AB - A microgap between implant and abutment can lead to mechanical and biological
problems such as abutment screw fracture and peri-implantitis. The aim of this
study was to evaluate microgap size and microbial leakage in the connection area
of 4 different abutments to ITI implants. In this experimental study, 36
abutments in 4 groups (including Cast On, Castable, Solid, and Synocta abutments)
connected to Straumann fixtures (with their inner part inoculated with bacterial
suspension) and microbial leakage were assessed at different times. The size of
the microgap in 4 randomized locations was then measured by scanning electron
microscope. The data were analyzed by SPSS software and by 1-way variance
statistical test, Kruskal-Wallis, and their supplementary tests (Mann-Whitney HSD
and Tukey's; alpha = .05) at the next step. The effect of using different types
of abutments was significant on the mean microgap size (P < .001) and on the mean
number of leaked colonies (CFU/mL) through the connection area of the implant and
abutment within the first 5 hours of the experiment (P = .012); however, it did
not significantly influence microleakage at 24 hours, 48 hours, and 14 days (P =
.145). Using Synocta abutments compared with Solid abutments will not provide us
with more accommodation, and vice versa. Using Solid and Synocta abutments can
significantly decrease the microgap size; however, Cast On abutments do not show
a significant difference in terms of microgap compared with Castable abutments.
Microleakage in the connection area is comparable for these 4 abutments.
PMID- 22047450
TI - Age-dependent deterioration of peak inspiratory flow with two kinds of dry powder
corticosteroid inhalers (Diskus and Turbuhaler) and relationships with asthma
control.
AB - BACKGROUND: Inhaled corticosteroid (ICS) therapy has improved the quality of life
(QOL) for many asthmatics and reduced mortality rates associated with asthma.
However, some patients do not obtain therapeutic benefit despite satisfactory
adherence. OBJECTIVES: To determine whether asthmatic patients were using ICS
devices appropriately, and to clarify relationships between these results and
QOL. SUBJECTS AND METHODS: We studied 100 adult asthmatics, divided into two
groups: 50 patients consecutively registered as using Diskus (fluticasone; D
group) and 50 consecutively registered as using Turbuhaler (budesonide; T-group).
We measured peak inspiratory flows (PIFs) using the In-Check Dial device.
Subjects also completed the Asthma Control Test for evaluation of QOL. RESULTS:
In the D-group, no patients showed PIF below the optimal range (30-90 L/min),
whereas 52% of patients had PIF>=91 L/min. In the T-group, 6% of patients showed
PIF over the optimal range (60-90 L/min), and 44% had PIF<=59 L/min. When
patients in the T-group were required to deliberately make a maximal inhalation,
14% still had PIF<=59 L/min. The proportion of patients with poor control was
significantly greater in the T-group than in the D-group. According to univariate
logistic regression analyses, low PIF tended to be associated with poor asthma
control in the T-group. No significant correlation was found between PIF and age
in the D-group, but PIF decreased significantly with age in the T-group.
CONCLUSIONS: Appropriate measures for patients in whom PIF has been judged as
lower than optimal include adequate education for inhalation and/or changing to a
different inhalation device. These measures should be kept in mind for elderly
asthma patients in particular, where appropriate selection of a corticosteroid
inhalation device in the early stages of therapy would also be important.
PMID- 22047451
TI - Physicians' knowledge of inhaler devices and inhalation techniques remains poor
in Spain.
AB - BACKGROUND: Studies in many countries in the 1990s revealed deficiencies in
physicians' knowledge about inhalation therapy. In an attempt to remedy this
situation, Spanish scientific societies implemented a variety of educational
strategies. The objective of the present study was to assess changes in attitudes
and knowledge about inhalers and inhalation techniques in a sizable sample of
physicians. METHODS: An 11-question multiple choice test was developed and
administered throughout Spain to practicing physicians from specialties that
frequently prescribe inhaler devices. The survey collected demographic
characteristics (four items), preferences (two items), and issues related to
knowledge (three items) and education (two items) about devices and inhalation
techniques. Completion of the questionnaire was voluntary, individual, and
anonymous. RESULTS: A total of 1514 respondents completed the questionnaire. Dry
powder inhalers (DPI) were preferred by 61.2% physicians, but only 46.1%
identified "inhale deeply and forcefully" as the most significant step in the
inhalation maneuver using these devices. Only 27.7% stated that they always
checked the patient's inhalation technique when prescribing a new inhaler. A
composite variable, general inhaled therapy knowledge, which pooled the correct
answers related to knowledge, revealed that only 14.2% physicians had an adequate
knowledge of inhaled therapy. Multivariate analysis showed that this knowledge
was lowest among internal medicine and primary care physicians. CONCLUSIONS:
Prescribers' knowledge of inhalers and inhalation techniques remains poor in
Spain. The causes should be identified in further research to allow effective
educational strategies to be developed. Specific educational policies should be
addressed to general practitioners.
PMID- 22047452
TI - Dietary fat intake and quality of life: the SUN project.
AB - BACKGROUND: Few studies have related nutritional factors with quality of life in
healthy populations. The purpose of the study was to assess whether dietary fat
intake is associated to mental and physical quality of life. METHODS: This
analysis included 8,430 participants from the SUN (Seguimiento Universidad de
Navarra) Project. The intake of saturated fatty acids (SFA), polyunsaturated
fatty acids (PUFA), trans unsaturated fatty acids (TFA), and monounsaturated
fatty acids (MUFA) was assessed through a 136-item food frequency questionnaire
at baseline. Quality of life was measured with the SF-36 Health Survey after 4
years of follow-up. Generalized Linear Models were fitted to assess the
regression coefficients (b) and their 95% confidence intervals (95% CI) for the 8
domains of the SF-36 according to successive quintiles of each kind of fatty
acids intake. RESULTS: The multivariate-adjusted models revealed a significant
inverse association for SFA intake (in quintiles) and two of the physical domains
(physical functioning and general health). E.g. for general health domain:
(highest quintile of intake (Q5) vs. lowest quintile (Q1), b = -1.6; 95% CI =
3.1, -0.1. General health also showed a dose-response relationship (p for trend <
0.05). For TFA intake (in quintiles), a significant inverse association was found
for most of the mental domains (vitality, social functioning and role emotional).
E.g. for vitality domain (Q5) vs. (Q1), b = -2.0, 95% CI = -3.4 to -0.6. We also
found an inverse association between TFA intake and the bodily pain domain: (Q5
vs. Q1), b = -2.6; 95% CI = -4.4 to -0.8, with a statistically significant dose
response relationship (p for trend < 0.05). Except for TFA intake and the mental
domains, the rest of the associations were attenuated when we repeated the
analysis adjusting for adherence to the Mediterranean diet. CONCLUSIONS: A
detrimental relationship between TFA intake at baseline and most of the SF-36
mental domains measured 4 years later were found, whereas weak inverse
associations were found for SFA intake and some physical domains.
PMID- 22047453
TI - Quantifying protein-protein interactions within noncovalent complexes using
electrospray ionization mass spectrometry.
AB - Several electrospray-mass spectrometry (ESI-MS)-based methods are available for
determining the constant of association (K(a)) between a protein and a small
ligand, but current MS-based strategies are not fully adequate for measuring K(a)
of protein-protein interactions accurately. We expanded the application of ESI-MS
based titration to determine the strength of noncovalent interactions between
proteins, forming a complex. Taking into account relative response factors
(probability of being ionized, transmitted, and detected), we determined K(a)
values of an equilibrium between dimers and tetramers at three different pH
values (6.8, 3.4, and 8.4). We investigated the association of the lectin
concanavalin A, whose dimer-tetramer ratio in the gas phase is affected by
solution concentration and by pH. To calculate the constants of association in
solution, we also utilized isothermal titration calorimetry (ITC) for a
comparison with MS-based titration. At pH 6.8 and pH 8.4, the K(a) values
measured by MS and by ITC were in agreement. ITC results allowed us to restrain
the response factor to a value close to 4. At pH 3.4, we were able to measure the
K(a) only by MS, but not by ITC because of limited sensitivity of calorimetry.
Our investigation illustrates the great potential MS for calculating the binding
strength of protein-protein interactions within noncovalent complexes. The main
advantages of MS over ITC are its sensitivity (i.e., the required amount of
sample is >100 times less than the one necessary for ITC), and the possibility to
obtain precise information on composition of protein complexes, their
stoichiometry, their subunit interactions, and their assembly pathway. Compared
to previous investigations, our study shows the strong influence of response
factors on determining accurate protein-protein association constants by MS.
PMID- 22047454
TI - Information processing speed, neural efficiency, and working memory performance
in multiple sclerosis: differential relationships with structural magnetic
resonance imaging.
AB - Multiple sclerosis (MS), a central nervous system (CNS) neurodegenerative
disorder, involves lesions of both white and gray matter and reported cognitive
impairments that include processing speed (PS), executive function, and working
memory (WM). This study closely examined the specifics of these cognitive
deficits and their relationship to structural brain damage. A visual n-back task
with 3 WM load conditions was used to assess WM performance (task accuracy), PS
(reaction time, RT), and a novel measure of processing efficiency (standard
deviation of RT, RTSD) in MS patients and controls. These behavioral measures
were related to quantitative magnetic resonance imaging (MRI) measures of white
and gray matter integrity. Even when MS patients performed as well as controls,
as seen for low WM load (0-back), they responded more slowly and were less
efficient in their speed of responding. Accuracy findings indicated that the
correct match trials were superior to correct nonmatch trials at differentiating
MS patients from controls. Further, decreased accuracy during the highest WM load
condition was associated with global damage that included both gray and white
matter atrophy, while slowed PS and particularly processing inefficiency were
associated primarily with white matter atrophy in MS. Importantly, relationships
between PS, processing efficiency, performance accuracy, and structural MRI
measures were seen only during the highest WM load condition, the condition that
required the most executive control. These findings suggest that the
MRI/behavioral relationships that were present exclusively during the 2-back
condition may reflect connectivity involving frontal cortical systems, the site
for executive control.
PMID- 22047455
TI - General pathway toward crystalline-core micelles with tunable morphology and
corona segregation.
AB - We present a general mechanism for the solution self-assembly of crystalline-core
micelles (CCMs) from triblock copolymers bearing a semicrystalline polyethylene
(PE) middle block. This approach enables the production of nanoparticles with
tunable dimensions and surface structures. Depending on the quality of the
solvent used for PE, either spherical or worm-like CCMs can be generated in an
easy and highly selective fashion from the same triblock copolymers via
crystallization-induced self-assembly upon cooling. If the triblock copolymer
stays molecularly dissolved at temperatures above the crystallization temperature
of the PE block, worm-like CCMs with high aspect ratios are formed by a
nucleation and growth process. Their length can be conveniently controlled by
varying the applied crystallization temperature. If exclusively spherical
micelles with an amorphous PE core are present before crystallization, confined
crystallization within the cores of the preformed micelles takes place and
spherical CCMs are formed. For polystyrene-block-polyethylene-block-poly(methyl
methacrylate) triblock terpolymers a patch-like microphase separation of the
corona is obtained for both spherical and worm-like CCMs due to the
incompatibility of the PS and PMMA blocks. The structure of the patch-like corona
depends on the selectivity of the employed solvent for the PS and PMMA corona
blocks, whereby nonselective solvents produce a more homogeneous patch size and
distribution. Annealing of the semicrystalline PE cores results in an
increasingly uniform crystallite size distribution and thus core thickness of the
worm-like CCMs.
PMID- 22047457
TI - FTIR and UV spectroscopy in real-time monitoring of S. cerevisiae cell culture.
AB - A combination of FTIR and UV spectroscopy is proposed as a novel technique for
integrated real-time monitoring of metabolic activity and growth rates of cell
cultures, required for systematic studies of cellular low-frequency (LF) electric
and magnetic field (EMF) effects. As an example, we investigated simultaneous
influence of periodic LF 3D EMFs on a culture of Saccharomyces cerevisiae
(baker's yeast) cells. Amplitudes, frequencies and phases of the field components
were the variable parameters. Electromagnetic fields were found to efficiently
control the activity of the yeast cells, with the resulting CO(2) production
rates, as monitored by FTIR spectroscopy, varying by at least one order of
magnitude due to the field action. Additionally, population dynamics of the yeast
cells was monitored by UV absorption of the yeast culture at lambda(prob) = 320
nm, and compared to the CO(2) production rates. The detected physiologically
active frequencies are all below 1 kHz, namely, 800 Hz excitation was effective
in reducing the metabolic rates and arresting cell proliferation, whereas 200 Hz
excitation was active in accelerating both cell proliferation and overall
metabolic rates. The proposed methods produce objective, reliable and
quantitative real-time results within minutes and may be used in various tasks
that could benefit from a rapid feedback they provide in the form of metabolic
and growth rates. Amplitude and frequency dependences of the LF EMF effects from
individual field components with different polarizations were recorded and
qualitatively interpreted based on a simple model, describing ion diffusion
through a membrane channel.
PMID- 22047458
TI - Planarian activity differences when maintained in water pre-treated with magnetic
fields: a nonlinear effect.
AB - There have been multiple claims that exposing water to a static magnetic field
affects its properties which influence living systems. To test this hypothesis,
planarian subsequent to dissection were maintained in spring water that had been
previously exposed for only one day to one of three (16, 160, or 1,600 G)
intensity static magnetic fields or to a reference condition. Although there was
no significant difference in regeneration rates over the subsequent seven-day
period, there was a statistically significant nonlinear effect for planarian
mobility and diffusion rates. Both mobility rates and diffusion velocity of a
liquid within the water that had been exposed to the 16 G field was about twice
that for water exposed to the other intensities. These results imply that
nonlinear biophysical effects may emerge under specific conditions of intensity
ranges for particular volumes of water.
PMID- 22047459
TI - MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis.
AB - Male Sprague Dawley rats were exposed to EMP irradiation of 100 kV/m peak-to-peak
e-field intensity and different numbers of pulses. Rat sperm samples were
prepared for analysis of sperm qualities; Testes were assessed by transmission
electron microscopy and serum hormone concentrations were examined by
radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and
manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc
superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were
also determined. EMP irradiation did not affect spermatozoon morphology,
micronucleus formation rate, sperm number or viability, but the acrosin reaction
rate decreased at 24 h and 48 h and recovered by 72 h after irradiation as
compared to the controls. The ultrastructure of rat testis displayed more serious
damage at 24 h than at other time points (6 h, 12 h, 48 h). Serum levels of
luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats
as compared to controls. After irradiation, enzymatic activities of T-SOD and
MnSOD were reduced by 24 h, consistent with the changes observed in MnSOD mRNA
expression; MDA content increased at 6 h in turn. These studies have quantified
the morphological damage and dysfunction in the rat reproductive system induced
by EMP. The mechanism of EMP induced damage may be associated with the inhibition
of MnSOD expression.
PMID- 22047460
TI - 900-MHz microwave radiation promotes oxidation in rat brain.
AB - Recently, there have been several reports referring to detrimental effects due to
radio frequency electromagnetic fields (RF-EMF) exposure. Special attention was
given to investigate the effect of mobile phone exposure on the rat brain. Since
the integrative mechanism of the entire body lies in the brain, it is suggestive
to analyze its biochemical aspects. For this, 35-day old Wistar rats were exposed
to a mobile phone for 2 h per day for a duration of 45 days where specific
absorption rate (SAR) was 0.9 W/Kg. Animals were divided in two groups: sham
exposed (n = 6) and exposed group (n = 6). Our observations indicate a
significant decrease (P < 0.05) in the level of glutathione peroxidase,
superoxide dismutase, and an increase in catalase activity. Moreover, protein
kinase shows a significant decrease in exposed group (P < 0.05) of hippocampus
and whole brain. Also, a significant decrease (P < 0.05) in the level of pineal
melatonin and a significant increase (P < 0.05) in creatine kinase and caspase 3
was observed in exposed group of whole brain as compared with sham exposed.
Finally, a significant increase in the level of ROS (reactive oxygen species) (P
< 0.05) was also recorded. The study concludes that a reduction or an increase
in antioxidative enzyme activities, protein kinase C, melatonin, caspase 3, and
creatine kinase are related to overproduction of reactive oxygen species (ROS) in
animals under mobile phone radiation exposure. Our findings on these biomarkers
are clear indications of possible health implications.
PMID- 22047461
TI - Numerical sensitivity modeling for the detection of skin tumors by using
tetrapolar probe.
AB - The measurement of electrical impedance of skin using surface electrodes permits
the assessment of changes in local properties of the skin and can be used in the
detection of tumors. The sensitivity of this technique depends mainly on the
geometry of the probe and the size of the tumor. In this article, the impedance
method was used to estimate the sensitivity of a tetrapolar probe in detecting
small regions of increased conductivity in a stratified model of human skin. The
impedance method was used to model the potential distribution using fasorial
analysis to solve the node equations of the equivalent circuit. Interpolation was
applied to reduce discretization error. The skin was modeled as a three-layer
structure with different conductivity and permittivity obtained from the
literature. A tumor was modeled as a small volume with admittivity four times
higher than the normal tissue. Sensitivity calculation was made as a function of
electrode diameter and separation, tumor size, and excitation frequency. The
simulations indicated that by inserting a one square millimeter tumor in the
epidermis, the load impedance to the current source varies about 1% while the
transfer impedance varied 8%. The sensitivity also increases nonlinearly with
increasing tumor area and thickness. Additionally, it was found that the
sensitivity of the transfer impedance has a maximum value when the electrodes are
separated by 1.8 mm. The results show that transfer impedance measurements of the
skin may detect small skin tumors with a reasonable sensitivity by using an
appropriate tetrapolar probe.
PMID- 22047462
TI - Analysis of DNA fragmentation in mouse embryos exposed to an extremely low
frequency electromagnetic field.
AB - Effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on DNA
damage in biological systems are still a matter of dispute. The aim of the
present study was to investigate the possible effect of electromagnetic field
exposure on DNA fragmentation in cells (blastomers) of mouse blastocysts. Eighty
female NMRI mice were randomly divided into 2 groups of 40 animals each. The
control group was left unexposed whereas the animals in the EMF-group were
exposed to a 50-Hz EMF at 0.5 mT 4 h per day, 6 days a week for a duration of 2
weeks. After the 8(th) day of exposure, the female mice in both groups were
superovulated (with injections of pregnant mare serum gonadotropin and human
chorionic gonadotropin) and then mated overnight. At approximately 4 days after
mating (102 h after the human chorionic gonadotropin treatment), blastocysts were
obtained by flushing the uterus horns. The mean numbers of pregnant mice,
blastocysts after flushing, blastomers within the blastocysts, and the DNA
fragmentation index following staining in both groups were compared using
statistical methods (SPSS, the Chi-square test, the Student's t-test and the Mann
Whitney U-test, P < 0.05). The results showed that the mean number of blastocysts
after flushing was significantly decreased in the EMF-group compared to that of
the control group (P < 0.03). The DNA fragmentation index was significantly
increased in the EMF-group compared to control (10.53% vs. 7.14%; P < 0.001).
However, there was no significant difference in the mean numbers of blastomers
and numbers of pregnant mice between the EMF-exposed and control group. Our
findings indicate that the EMF exposure in preimplantation stage could have
detrimental effects on female mouse fertility and embryo development by
decreasing the number of blastocysts and increasing the blastocysts DNA
fragmentation.
PMID- 22047463
TI - Effects of radiofrequency radiation exposure on blood-brain barrier permeability
in male and female rats.
AB - During the last several decades, numerous studies have been performed aiming at
the question of whether or not exposure to radiofrequency radiation (RFR)
influences the permeability of the blood-brain barrier (BBB). The objective of
this study was to investigate the effect of RFR on the permeability of BBB in
male and female Wistar albino rats. Right brain, left brain, cerebellum, and
total brain were analyzed separately in the study. Rats were exposed to 0.9 and
1.8 GHz continuous-wave (CW) RFR for 20 min (at SARs of 4.26 mW/kg and 1.46
mW/kg, respectively) while under anesthesia. Control rats were sham-exposed.
Disruption of BBB integrity was detected spectrophotometrically using the Evans
blue dye, which has been used as a BBB tracer and is known to be bound to serum
albumin. Right brain, left brain, cerebellum, and total brain were evaluated for
BBB permeability. In female rats, no albumin extravasation was found in in the
brain after RFR exposure. A significant increase in albumin was found in the
brains of the RF-exposed male rats when compared to sham-exposed male brains.
These results suggest that exposure to 0.9 and 1.8 GHz CW RFR at levels below the
international limits can affect the vascular permeability in the brain of male
rats. The possible risk of RFR exposure in humans is a major concern for the
society. Thus, this topic should be investigated more thoroughly in the future.
PMID- 22047464
TI - Selection of suitable reference genes from bone cells in large gradient high
magnetic field based on GeNorm algorithm.
AB - Studies of animals and humans subjected to spaceflight demonstrate that
weightlessness negatively affects the mass and mechanical properties of bone
tissue. Bone cells could sense and respond to the gravity unloading, and genes
sensitive to gravity change were considered to play a critical role in the
mechanotransduction of bone cells. To evaluate the fold-change of gene
expression, appropriate reference genes should be identified because there is no
housekeeping gene having stable expression in all experimental conditions.
Consequently, expression stability of ten candidate housekeeping genes were
examined in osteoblast-like MC3T3-E1, osteocyte-like MLO-Y4, and preosteoclast
like FLG29.1 cells under different apparent gravities (MUg, 1 g, and 2 g) in the
high-intensity gradient magnetic field produced by a superconducting magnet. The
results showed that the relative expression of these ten candidate housekeeping
genes was different in different bone cells; Moreover, the most suitable
reference genes of the same cells in altered gravity conditions were also
different from that in strong magnetic field. It demonstrated the importance of
selecting suitable reference genes in experimental set-ups. Furthermore, it
provides an alternative choice to the traditionally accepted housekeeping genes
used so far about studies of gravitational biology and magneto biology.
PMID- 22047466
TI - Effect of an institutional development plan for user participation on
professionals' knowledge, practice, and attitudes. A controlled study.
AB - BACKGROUND: Governments in several countries attempt to strengthen user
participation through instructing health care organisations to plan and implement
activities such as user representation in administrational boards, improved
information to users, and more individual user participation in clinical work.
The professionals are central in implementing initiatives to enhance user
participation in organisations, but no controlled studies have been conducted on
the effect on professionals from implementing institutional development plans.
The objective was to investigate whether implementing a development plan
intending to enhance user participation in a mental health hospital had any
effect on the professionals' knowledge, practice, or attitudes towards user
participation. METHODS: This was a non-randomized controlled study including
professionals from three mental health hospitals in Central Norway. A development
plan intended to enhance user participation was implemented in one of the
hospitals as a part of a larger re-organizational process. The plan included i.e.
establishing a patient education centre and a user office, purchasing of user
expertise, appointing contact professionals for next of kin, and improving of the
centre's information and the professional culture. The professionals at the
intervention hospital thus constituted the intervention group, while the
professionals at two other hospitals participated as control group. All
professionals were invited to answer the Consumer Participation Questionnaire
(CPQ) and additional questions, focusing on knowledge, practice, and attitudes
towards user participation, two times with a 16 months interval. RESULTS: A total
of 438 professionals participated (55% response rate). Comparing the changes in
the intervention group with the changes in the control group revealed no
statistically significant differences at a 0.05 level. The implementation of the
development plan thus had no measurable effect on the professionals' knowledge,
practice, or attitudes at the intervention hospital, compared to the control
hospitals. CONCLUSION: This is the first controlled study on the effect on
professionals from implementing a development plan to enhance user participation
in a mental health hospital. The plan had no effect on professionals' knowledge,
practice, or attitudes. This can be due to the quality of the development plan,
the implementation process, and/or the suitability of the outcome measures.
PMID- 22047467
TI - Solvent evaporation induced aggregating assembly approach to three-dimensional
ordered mesoporous silica with ultralarge accessible mesopores.
AB - A solvent evaporation induced aggregating assembly (EIAA) method has been
demonstrated for synthesis of highly ordered mesoporous silicas (OMS) in the
acidic tetrahydrofuran (THF)/H(2)O mixture by using poly(ethylene oxide)-b
poly(methyl methacrylate) (PEO-b-PMMA) as the template and
tetraethylorthosilicate (TEOS) as the silica precursor. During the continuous
evaporation of THF (a good solvent for PEO-b-PMMA) from the reaction solution,
the template molecules, together with silicate oligomers, were driven to form
composite micelles in the homogeneous solution and further assemble into large
particles with ordered mesostructure. The obtained ordered mesoporous silicas
possess a unique crystal-like morphology with a face centered cubic (fcc)
mesostructure, large pore size up to 37.0 nm, large window size (8.7 nm), high
BET surface area (508 m(2)/g), and large pore volume (1.46 cm(3)/g). Because of
the large accessible mesopores, uniform gold nanoparticles (ca. 4.0 nm) can be
introduced into mesopores of the OMS materials using the in situ reduction
method. The obtained Au/OMS materials were successfully applied to fast catalytic
reduction of 4-nitrophenol in the presence of NaHB(4) as the reductant. The
supported catalysts can be reused for catalytic reactions without significant
decrease in catalysis performance even after 10 cycles.
PMID- 22047469
TI - The role of triplet state keto-enol tautomerism in the photodeamination of
metamitron.
AB - Substituted 4-amino-1,2,4-triazin-5-ones undergo photodeamination through
cleavage of the N-NH(2) bond in the presence of oxygen and water. To elucidate
the mechanism of this reaction, we investigated the photolysis of metamitron (4
amino-6-phenyl-3-methyl-1,2,4-triazin-5-one) by nanosecond laser flash
photolysis, steady-state irradiation, and ab initio calculations. Upon pulsed
laser excitation of deoxygenated aqueous metamitron, two transient species are
clearly detected. The predictions of ab initio results are consistent with
experimental results: (i) it is proposed here that the transient species are,
respectively, the keto and diradical forms of the metamitron keto-enol
tautomerism in the triplet state, and (ii) in water, the activation free energy
barrier of enolization is drastically decreased. Thus, the formation of the
diradical triplet is enabled in aqueous solvent. A detailed analysis of the
intermediate structures that lead to the final products (HNO(2) and
deaminometamitron) is provided.
PMID- 22047468
TI - A patient with amyotrophic lateral sclerosis and atypical clinical and
electrodiagnostic features: a case report.
AB - INTRODUCTION: Amyotrophic lateral sclerosis is a rapidly progressive, fatal
neurodegenerative disorder for which there is no effective treatment. The
diagnosis is dependent on the clinical presentation and consistent
electrodiagnostic studies. Typically, there is a combination of upper and lower
motor neuron signs as well as electrodiagnostic studies indicative of diffuse
motor axonal injury. The presentation of amyotrophic lateral sclerosis, however,
may be variable. At the same time, the diagnosis is essential for patient
prognosis and management. It is therefore important to appreciate the range of
possible presentations of amyotrophic lateral sclerosis. CASE PRESENTATION: We
present the case of a 57-year-old Caucasian man with pathological findings on
postmortem examination consistent with amyotrophic lateral sclerosis but atypical
clinical and electrodiagnostic features. He died after a rapid course of
progressive weakness. The patient did not respond to immunosuppressive therapy.
CONCLUSION: Amyotrophic lateral sclerosis should be considered in patients with a
rapidly progressive, unexplained neuropathic process. This should be true even if
there are atypical clinical and electrodiagnostic findings. Absence of response
to therapy and the development of upper motor neuron signs should reinforce the
possibility that amyotrophic lateral sclerosis may be present. Since amyotrophic
lateral sclerosis is a fatal illness, however, the possibility of this disease in
patients with atypical clinical features should not diminish the need for a
thorough diagnostic evaluation and treatment trials.
PMID- 22047471
TI - From idealistic helper to enterprising learner: critical reflections on personal
development through experiences from Afghanistan.
AB - There is little written about the cultural, social, and ethical challenges
encountered by physiotherapists engaging in development work. This article takes
a critical perspective on what it means to engage in development work as an
expatriate physiotherapist, through a self-critical reflection on experiences
from Afghanistan. The field notes from an ethnographic study of a development
project conducted in Afghanistan were analysed to explore the transformative
process of personal and professional development of the development worker. The
critical reflective process entailed a change in meaning perspective, described
as a shift from the position of an Idealistic Helper to an Enterprising Learner.
Of importance in this process were "disorienting dilemmas" that challenged
personal perceptions. Critical reflection over such dilemmas led to deeper
understanding facilitating the process of change. The essential lesson learned is
that the baseline for understanding others is an understanding of one's own
meaning perspectives and manner of participation in relation to others and their
context. The insights gained have implications for physiotherapists working in
development contexts, for other development workers, and for physiotherapists
working with patients in clinical practice in a nondevelopment context. Exploring
how to collaborate in development contexts could be done using reflective groups
with expatriate and local physiotherapists and/or patients. This could lead to
greater understanding of oneself, each other, and the local context.
PMID- 22047472
TI - Chemical vapor deposition synthesis of tunable unsubstituted polythiophene.
AB - Despite having exceptional electroactive properties, applications of
unsubstituted polythiophene (PTh) have been limited due to its insolubility. To
overcome this challenge, we have employed oxidative chemical vapor deposition
(oCVD) as a unique liquid-free technique to enable the oxidative polymerization
of PTh using thiophene as the starting monomer and vanadium oxytrichloride as an
effective vaporizable oxidant initiator. Vibrational and phototelectron
spectroscopy indicated the formation of unsubstituted polythiophene. Cyclic
voltammetry revealed its electrochromic behavior in solution. Significantly,
polymer conjugation length and electrical conductivity can be tuned by
controlling oCVD process variables. Polymerization is found to be adsorption
limited, so by providing sufficient monomer and limiting the amount of initiator
at the growth surface, PTh is believed to be formed through alpha-alpha thiophene
linkages.
PMID- 22047473
TI - ERRATUM.
PMID- 22047477
TI - Structural optimization of Cu-Ag-Au trimetallic clusters by adaptive immune
optimization algorithm.
AB - The putative global minimum structures of Cu-Ag-Au trimetallic clusters with 19
and 55 atoms are obtained by adaptive immune optimization algorithm (AIOA) with
the Gupta potential. For the 19-atom trimetallic clusters, the results indicate
that all of them have double-icosahedral motifs. For the optimized structures of
Cu(13)Ag(n)Au(42-n) (n = 1-41), the clusters can be categorized into 19 Mackay
icosahedral structures, 1 6-fold pancake structure, and 21 ring-like structures
linked by three face-sharing double-icosahedra. Furthermore, the segregation
phenomena of the Cu, Ag, and Au atoms in the Cu-Ag-Au trimetallic clusters are
studied to provide useful information for geometric character. Results show that
Cu and Ag atoms prefer to locate in the inner-shell and on the surface,
respectively, whereas Au atoms mainly locate in the middle-shell and tend to
solve into Cu and Ag atoms.
PMID- 22047478
TI - Science convention "Rijeka and its Citizens in Medical History" 2000-2009 -
history of medicine as a component of scientific visibility.
AB - This paper analyses the form and content of the first ten science conventions
"Rijeka and its Citizens in Medical History" ("Rijeka i Rijecani u medicinskoj
povjesnici") which were held in the period between 2000 and 2009 according to the
archive data of the convention organizers Croatian Scientific Society for the
History of Health Culture. It presents data on the inception of the idea of a
science convention, its organisational features (organising committees, presiding
committees, convention topics, venue, patrons) and number of participants. A
total of 174 presentations whose abstracts were published in individual
Convention Collections were given at the ten conventions by 103 different authors
from Croatia and neighbouring countries. After the first ten years the entire
material was compiled and published with an analytical comment in the anniversary
issue Znanstveni skup Rijeka i Rijecani u medicinskoj povjesnici 2000-2009
(Scientific Convention Rijeka and its Citizens in Medical History 2000-2009)
within Biblioteka AMHA. Most of the papers printed in extenso are published in
the magazine AMHA - Acta medico historica Adriatica. The analysis of all
presentations provides quantity data on the number of presented papers, number of
presenters and number of co-authored papers, as well as quality determinants
within the evaluation of the achievement of science convention objectives. The
end gives a review of the significance of this convention within the regional,
national and international aspect.
PMID- 22047479
TI - Apothecary activity in Dubrovnik Dominican Monastery from 17th to the beginning
19th century.
AB - The origin of the Dominican monastery pharmacy is not clear, but sources suggest
that it had operated from the eve of the great earthquake in Dubrovnik in 1667 to
the beginning of the 19th century. Its last pharmacist, praised for his
competence, passed away in 1803, leaving no one behind The prior travelled all
the way to Naples to find a competent pharmacist in his stead, but never
returned. Story has it that on the way back, the abbot and the pharmacist lost
their lives in a shipwreck. The French army occupied the town in 1806, and the
monastery was turned into a military camp. Following the retreat of the French
army in 1814, the monastery was returned to the Dominicans, but the pharmacy was
never restored.
PMID- 22047480
TI - [Vampires in the village Zrnovo on the island of Korcula: following an archival
document from the 18th century].
AB - The main interest of this essay is the analysis of the document from the State
Archive in Venice (file: Capi del Consiglio de' Dieci: Lettere di Rettori e di
altre cariche) which is connected with the episode from 1748 when the inhabitants
of the village zrnove on the island of Korcula in Croatia opened tombs on the
local cemetery in the fear of the vampires treating. This essay try to show some
social circumstances connected with this event as well as a local vernacular
tradition concerning superstitions.
PMID- 22047481
TI - Health Resort Opatija Volunteer Fire Brigade and Rescue Society.
AB - Not only the health service but also several other humanitarian institutions and
societies were active in Abbazia/Opatija, the most important town on the once
Austrian Riviera, the town that was also known as the Austrian Nice. The most
important of the societies was The Health Resort Opatija Volunteer Fire Brigade
and Rescue Society. The authors of this article have been particularly interested
in the society's founding and its activity until it moved into the new building
at 6, St. Florjan's Street in 1910. The fast urbanisation and the development of
the industry raised the need of the well organised activity of putting out fires.
The German gymnastics societies were the first to include the education and the
skills development of the volunteer firemen into their programmes. The first
volunteer fire brigades appeared in Austria after 1863. The huge fire that broke
out in Vienna in 1881 showed that the fast and efficient rescuing demanded a well
prepared organization of a team of rescuers. Based on the initiative of the
chimney sweep Franz Drescher and The South Railway Company, the volunteer fire
brigade was founded in Opatija already in 1886. The founding of the volunteer
rescue society was based on the idea given by dr. Jaromir Mundy, the permanent
guest in Opatija and a friend of prof. dr. Theodor Billroth, in 1894. The
intertwining activity of the both societies resulted in their formal joining. The
head physician became dr. Franz Tripold, the chief commander was Franz Doberlet
junior. For his special merits, the general assembly of the Health Resort Opatija
Volunteer Fire Brigade and Rescue Society appointed him the honourable commander
of the society in 1903 and he received a special photo album with the photos of
the volunteer firemen and the rescuers' practice. The Emperor Franz Joseph I
Jubilee Fire Station, the Rescue Station And the Sanatorium (Kaiser Franz Joseph
I Jubilaums - Feuerwehrrustungshaus, Rettungsstation und Erholungsheim) was given
to the use on 1st October 1910. Since then, the two societies worked at this same
location. The Volunteer Fire Brigade Opatija has been located in this building
ever since.
PMID- 22047482
TI - [Dr Anto Maric (1897-1982): a journey from alcohology and dermatovenereology to
psychiatry and balneology].
AB - Dr Anto Maric (1897-1982) was born in Vuksic in Bosnia. He completed medical
studies in Vienna and Prague. He published his results from the Department for
dermatovenerology at Sarajevo State Hospital, Bosnia. He engaged himself in the
movement against alcoholism, too. Later he moved to the Neuropsychiatry ward in
Belgrade and was appointed manager in a new psychiatry hospital in Kovin, Serbia.
For years he had been a community physician in Stanisic in Vojvodina. During the
Second World War, he worked in the psychiatric hospital Vrapce at the outskirts
of Zagreb, Croatia and after the war he became the head of a thermal spa in
Srebrenica, Bosnia. After specialisation in balneology, he came to Rijeka to
overlook the reconstruction of a thermal spa near Buzet in Istria. He made use of
his long experience in dermatovenerology, neuropsychiatry and balneology to
promote the importance of the unity between physical and psychological for
maintaining human health.
PMID- 22047483
TI - Gout in the writings of eminent ancient Greek and Byzantine physicians.
AB - Gout is a medical condition with typical recurrent attacks of acute inflammatory
arthritis. The severity of this illness has been recognised from antiquity, and
several ancient physicians studied it intensively. This paper presents the
pathogenesis of the disease, approaches to therapy and preventive measures based
on a number of original medical scripts from Hippocrates to the end of the
Byzantine era.
PMID- 22047484
TI - Rufus of Ephesus and his contribution to the development of anatomical
nomenclature.
AB - Rufus of Ephesus, a famous ancient physician, lived about the years 80 - 150 CE.
His theories stressed the importance of anatomy and he preferred pragmatic
approach to diagnosis and treatment. In his work "On the Names of the Parts of
the Human Body", he put in pragmatic effort to make a lexicon of anatomy for his
pupils. In the introduction, he described it as a manual for the students of
medical art which relied on demonstration in teaching; visible (outer) parts of
the body were shown on a demonstrator and invisible (inner) parts were shown on a
dissected monkey. The brief explanation of the anatomical terms includes
position, shape, and functions of organs, and this is what makes his work a
pioneering effort to explain the anatomy clearly, systematically, and using
consistent terminology. Rufus stressed the importance of exact nomenclature to
prevent misunderstandings in medical practice. This anatomy manual had a major
influence on the development of anatomical terminology. It is an important
contribution to the history of teaching. The other essential contribution of
Rufus' lexicon (also known for its briefer title Onomastikon) is that the author
recognised and critically reviewed the knowledge and views of his predecessors,
physicians of the pre-Galenic period. No less important was his teaching to
anatomists and physicians who followed, as they often cited or paraphrased Rufus
in their own works (Galen, Oribasius). Many fragments of Rufus' work have been
preserved by medieval Arabic medical writers, especially by Rhazes.
PMID- 22047485
TI - [Dr Stanislav Zupic (1897-1973) - a remarkable figure in Croatian psychiatry].
AB - Stanislav Zupic (1897-1973) spent most of his career (1920-1962) in the
Psychiatric Hospital Vrapce, Zagreb, Croatia and was its 8th director from 1940
to 1941. He is remembered by a number innovations in treating psychoses, by a
pioneering Croatian psychodrama (in 1938, he published a play Coming back to
Life), and by introducing bibliotherapy, musical therapy, art therapy, and
homeopathy to treat mental illnesses. On his initiative, the psychiatric hospital
introduced treatment with insulin-provoked comma, convulsive therapy, Largactil,
and other state-of-the-art psychopharmaceuticals. In addition to treatment, he
provided forensic expertise. His free time he would spend writing pathographies
of artists and literary critics. In 1924, he was one of the founders of the
Yugoslav Anthroposophical Society Marija Sofija, which is still active in Zagreb.
From 1935, he had been collecting interesting exhibits for what was to become the
core of the hospital museum.
PMID- 22047486
TI - [Burn injuries: what have we learned from history].
AB - Severe burn injuries present a significant public health risk and are often
associated with a life-threatening systemic inflammatory response. With the
traditional approach, patients often stay in hospital longer and are more prone
to problems like joint contractures, hypertrophic scars and infections due to
delayed healing. The approach to burn injuries has been improving through and has
been adopting new technologies and materials. Today, burn injuries are treated by
general practitioners and surgeons. Unfortunately, this does not always ensure
faster healing improvement of the quality of life.
PMID- 22047487
TI - [The tragic demise of head physician Ortensio Pepi in Pula in 1938].
AB - The description represents a frame - an anecdotal one from today's perspective -
from the history of surgery in Pula, to which the author's attention was directed
by the late Vilijam Bilic, M.D., head of the Section for surgical diseases of the
General Hospital in Pula. Head physician Ortensio Pepi, head of surgery of the
then Regional Hospital, died in Pula on January 17, 1938 from gunshot wounds
inflicted ten days before. He was shot in the street by a husband of a patient
that died three months before following a difficult surgery. It appears that the
gunman passed judgement on himself immediately after the insane act by shooting
himself in the head, and died the same evening. The event garnered a lot of
attention from the only newspaper of the time in Pula - Corriere Istriano,
through which we keep track of the difficult, yet successful abdomen surgery and
the gradual recovery of head physician Pepi. However, several days after the
reporter published that the patient"s condition is no longer life threatening,
Ortensio Pepi died "due to complications".
PMID- 22047488
TI - Heart surgeon Miro Kosak (1919-2010) and his contribution to the development of
cardiovascular surgery in slovenia.
AB - Heart surgeon Miro Kosak was a pioneer of modern cardiovascular surgery in
Slovenia; in 1958, he performed the first open-heart surgery with extracorporeal
circulation, in 1965, the first implantation of heart valve and pacemaker, and in
1971, the first bypass on coronary arteries. He also paved the way for heart
transplantations that followed.
PMID- 22047489
TI - The cerebellum and neuropsychological functioning: a critical review.
AB - The cerebellum, while once considered a brain region principally involved in
motor control and coordination, is increasingly becoming associated with a range
of neuropsychological and neuropsychiatric presentations. This paper reviews the
dominant neuropsychological domains and neuropsychiatric conditions for which
cerebellar involvement has been demonstrated, including visuospatial functioning,
learning and memory, language, executive functioning, attention
deficit/hyperactivity disorder, autism spectrum disorders, and schizophrenia. The
paper concludes with a discussion of a potential neuropsychological localization
model within the cerebellum and a discussion of prognosis and rates of recovery
that can be expected, following localized cerebellar lesions.
PMID- 22047490
TI - Study of probe-sample distance for biomedical spectra measurement.
AB - BACKGROUND: Fiber-based optical spectroscopy has been widely used for biomedical
applications. However, the effect of probe-sample distance on the collection
efficiency has not been well investigated. METHOD: In this paper, we presented a
theoretical model to maximize the illumination and collection efficiency in
designing fiber optic probes for biomedical spectra measurement. This model was
in general applicable to probes with single or multiple fibers at an arbitrary
incident angle. In order to demonstrate the theory, a fluorescence spectrometer
was used to measure the fluorescence of human finger skin at various probe-sample
distances. The fluorescence spectrum and the total fluorescence intensity were
recorded. RESULTS: The theoretical results show that for single fiber probes,
contact measurement always provides the best results. While for multi-fiber
probes, there is an optimal probe distance. When a 400- MUm excitation fiber is
used to deliver the light to the skin and another six 400- MUm fibers surrounding
the excitation fiber are used to collect the fluorescence signal, the
experimental results show that human finger skin has very strong fluorescence
between 475 nm and 700 nm under 450 nm excitation. The fluorescence intensity is
heavily dependent on the probe-sample distance and there is an optimal probe
distance. CONCLUSIONS: We investigated a number of probe-sample configurations
and found that contact measurement could be the primary choice for single-fiber
probes, but was very inefficient for multi-fiber probes. There was an optimal
probe-sample distance for multi-fiber probes. By carefully choosing the probe
sample distance, the collection efficiency could be enhanced by 5-10 times. Our
experiments demonstrated that the experimental results of the probe-sample
distance dependence of collection efficiency in multi-fiber probes were in
general agreement with our theory.
PMID- 22047491
TI - Management of asthma in pregnant women by general practitioners: a cross
sectional survey.
AB - BACKGROUND: Poorly controlled asthma can lead to maternal and fetal
complications. Despite the known risks of poorly controlled asthma during
pregnancy and the need for stepping up therapy when appropriate, there are
concerns that management is suboptimal in primary care.Our objective was to
investigate the management of asthma during pregnancy by general practitioners
providing shared maternity care. METHODS: A pre-piloted, anonymous mail survey
was sent to all general practitioners (n = 842) involved in shared maternity care
at six maternity hospitals in Victoria, Australia. Respondents were asked about
their perceived safety of individual asthma medications during pregnancy.
Approach to asthma management during pregnancy was further explored using
scenarios of pregnant women with stable and deteriorating asthma and poor
medication adherence. RESULTS: Inhaled corticosteroids (ICS) were perceived to be
the safest and were the preferred preventive medication in first trimester
(74.1%), whilst leukotriene receptor antagonists were the least preferred (2.9%).
A quarter (25.8%) of respondents would stop or decrease patients' ICS doses
during pregnancy, even when their asthma was well controlled by current therapy.
In addition, 12.1% of respondents were not sure how to manage deteriorating
asthma during pregnancy and opted to refer to another health professional. Almost
half the respondents (48.9%) reported encountering medication nonadherence during
pregnancy. CONCLUSION: A lack of confidence and/or knowledge among general
practitioners in managing deteriorating asthma in pregnancy was observed despite
a good understanding of the safety of asthma medications during pregnancy,
compliance with evidence-based guidelines in the selection of preventive
medications, and self reported good asthma knowledge.
PMID- 22047492
TI - Nanocapsules based on linear and Y-shaped 3-miktoarm star-block PEO-PCL
copolymers as sustained delivery system for hydrophilic molecules.
AB - Well-defined amphiphilic Y-shaped miktoarm star-block copolymers of PEO and PCL
were synthesized by ring-opening polymerization of epsilon-caprolactone initiated
by a PEO-bound lysine macroinitiator. The copolymers were characterized by (1)H
NMR, SEC, DSC, and WAXD techniques. Separate PCL and PEO crystalline phases occur
in melt-crystallized copolymers when their segmental lengths were comparable and
the PCL content was <=80 wt %. Self-assembling of these copolymers in aqueous
medium led to nanoaggregates with low critical aggregation concentration values
(0.35 to 1.6 mg.L(-1)) and size depending on composition. Despite the fact that
copolymers were not prone to self-organize in vesicles, once processed by a novel
w/o emulsion-melting-sonication technique, they gave nanocapsules with a water
core and a hydrophilic surface. A macromolecular fluorescent dye was effectively
loaded and released at sustained rate by optimizing nanocapsule formulation. The
results demonstrate that amphiphilic block copolymers can be assembled in
different kinds of nanomorphologies independently of their
hydrophilic/hydrophobic balance and architecture through specifically designed
preparation techniques.
PMID- 22047493
TI - Functional analysis of UGT1A4(P24T) and UGT1A4(L48V) variant enzymes.
AB - AIM: To investigate the effects of two nonsynonymous SNPs, UGT1A4*2 (rs#:
6755571, 70C>A, P24T) and UGT1A4*3 (rs#: 2011425, 142T>G, L48V), on the function
of UGT1A4 against dihydrotestosterone (DHT), transandrosterone (t-AND),
lamotrigine (LTG) and tamoxifen (TAM). MATERIALS & METHODS: Detailed kinetic
experiments were conducted with recombinant UGT1A4(wild-type), UGT1A4(P24T) and
UGT1A4(L48V), which were overexpressed in HEK293 cell lines. The kinetic profiles
and kinetic parameters (K(m), V(max) and CL(int)) obtained with either
UGT1A4(P24T) or UGT1A4(L48V) were compared with those obtained with the wild-type
enzyme. The interaction of TAM on UG1A4-catalyzed DHT glucuronidation was also
investigated with the three UGT1A4 polymorphic enzymes. RESULTS: UGT1A4(L48V) had
higher enzyme efficiency (CL(int)) compared with wild-type UGT1A4 on DHT
glucuronidation; UGT1A4(P24T) and UGT1A4(L48V) had lower CL(int) than wild-type
UGT1A4 for t-AND and LTG glucuronidation. The TAM CL(int) with UGT1A4(P24T) and
UGT1A4(L48V) glucuronidation and the UGT1A4(P24T)-catalyzed DHT glucuronidation
were, on the other hand, similar to those of the wild-type enzyme. With all three
enzymes, TAM activated UGT1A4-catalyzed DHT glucuronidation in a concentration
dependent fashion. CONCLUSION: Decreased CL(int) of UGT1A4(P24T) and UGT1A4(L48V)
on LTG glucuronidation may lead to interindividual variations in LTG metabolism
in vivo. However, it is less likely that these polymorphisms would have impact on
DHT and t-AND metabolism in vivo because these compounds are glucuronidated by
multiple enzymes.
PMID- 22047494
TI - Editorial.
PMID- 22047495
TI - Nicolaas Adriaan van der Velden (1927-1979).
PMID- 22047496
TI - Investigation of protein conformational stability employing a multimodal
spectrometer.
AB - The conformational stability of proteins is typically investigated by use of a
variety of biophysical measurements as a function of environmental stresses such
as pH and temperature. Thus, multiple experiments are required on a variety of
instruments, each providing information on a particular aspect of a protein's
higher order structural integrity. These measurements typically require large
sample quantities and long experimental times. In this study, a new methodology
is described to obtain protein conformational stability data simultaneously,
including UV absorption, light scattering, and near- and far-UV circular
dichroism, by employing a multimodal spectrometer. Fluorescence spectral data are
also collected on the same instrument, although not simultaneously. The method
was developed by examining the thermal and pH stability of four model proteins.
Results showed reproducible and accurate results from this single instrument, and
data collection was rapid with minimal protein sample requirements. We illustrate
the application of this method to the generation of empirical phase diagrams
(EPDs) to better characterize the overall conformational stability of proteins.
This new approach facilitates the rapid characterization of protein structure and
stability in a single methodology, useful for analysis of unknown proteins as
well as screening of solution conditions to optimize stability for protein
therapeutic drug candidates.
PMID- 22047498
TI - High prevalence of HPV in non-cervical sites of women with abnormal cervical
cytology.
AB - BACKGROUND: Human papillomaviruses (HPV) are causally associated with ano-genital
and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and
head and neck cancers have now been demonstrated in the developed world over the
last decade. The majority of published data on HPV prevalence at the anal and oro
pharyngeal sites are from studies of higher-risk populations. There is a paucity
of data on the prevalence of HPV at non-cervical sites in lower risk, non-HIV+
women and this study was designed to provide initial pilot data on a population
of women recalled for colposcopy as part of the UK cervical screening programme.
METHODS: 100 non-HIV+ women with abnormal cervical cytology, attending clinic for
colposcopic examination were recruited. Swabs from the oro-pharyngeal, anal and
cervical sites were taken and DNA extracted. HPV detection and genotyping were
performed using a standardised, commercially available PCR-line blot assay, which
is used to genotype 37 HPV subtypes known to infect the ano-genital and oro
pharyngeal areas. Strict sampling and laboratory precautions were taken to
prevent cross-contamination. RESULTS: There was a very high prevalence of HPV
infection at all three sites: 96.0%, 91.4% and 92.4% at the cervix, anus and oro
pharynx, respectively. Multiple HPV subtype infections were dominant at all 3
mucosal sites. At least one or more HR genotype was present at both the
cervix/anus in 39/52 (75.0%) patients; both the cervix/oro-pharynx in 48/56
(85.7%) patients; and both the anus/oro-pharynx in 39/52 (75.0%) patients. HPV 16
infection was highly dominant across all mucosal sites, with over a 2-fold
increase over the next most prevalent subtype (HPV 31). CONCLUSIONS: Women with
abnormal smears have widespread infection with high-risk HPV at the cervical,
anal and oro-pharyngeal mucosal sites and may represent a higher risk population
for HPV disease in the future.
PMID- 22047499
TI - Bacteriophage lysis of Enterococcus host strains: a tool for microbial source
tracking?
AB - This paper describes the isolation of Enterococcus host strains, for potential
use as simple bacteriophage (phage)-based microbial source tracking (MST) tools.
Presumptive Enterococcus host strains were isolated from cattle feces, raw
municipal wastewater, agricultural runoff, and waters impacted by farms or
wastewater treatment works (WWTW) in southern England, United Kingdom (UK). All
enterococcal host strains (n = 390) were first screened for their ability to
detect phage in samples of raw municipal wastewater and fecal material from
cattle, pigs, and sheep. Host strains that detected phage (n = 147) were ranked
according to both their specificity to a particular fecal source and also the
number of phages (expressed as plaque-forming units, PFU) that they detected per
milliliter of sample. Host strains that demonstrated host specificity and which
detected phages at levels greater than 100 PFU/mL (n = 29) were further tested
using additional fecal samples of human and nonhuman origin. The specificity and
sensitivity of the enterococcal host strains were found to vary, ranging from 44
to 100% and from 17 to 83%, respectively. Most notably, seven strains exhibited
100% specificity to either cattle, human, or pig samples. Isolates exhibiting
specificity to cattle were identified as belonging to the species Enterococcus
casseliflavus , Enterococcus mundtii , or Enterococcus gallinarum , while human
and pig isolates were members of either Enterococcus faecium or Enterococcus
faecalis . The high specificity of phages infecting Enterococcus hosts and the
simplicity and relatively low cost of the approach collectively indicate a strong
potential for using this method as a tool in MST.
PMID- 22047500
TI - QTL detection for Aeromonas salmonicida resistance related traits in turbot
(Scophthalmus maximus).
AB - BACKGROUND: Interactions between fish and pathogens, that may be harmless under
natural conditions, often result in serious diseases in aquaculture systems. This
is especially important due to the fact that the strains used in aquaculture are
derived from wild strains that may not have had enough time to adapt to new
disease pressures. The turbot is one of the most promising European aquaculture
species. Furunculosis, caused by the bacterium Aeromonas salmonicida, produces
important losses to turbot industry. An appealing solution is to achieve more
robust broodstock, which can prevent or diminish the devastating effects of
epizooties. Genomics strategies have been developed in turbot to look for
candidate genes for resistance to furunculosis and a genetic map with appropriate
density to screen for genomic associations has been also constructed. In the
present study, a genome scan for QTL affecting resistance and survival to A.
salmonicida in four turbot families was carried out. The objectives were to
identify consistent QTL using different statistical approaches (linear regression
and maximum likelihood) and to locate the tightest associated markers for their
application in genetic breeding strategies. RESULTS: Significant QTL for
resistance were identified by the linear regression method in three linkage
groups (LGs 4, 6 and 9) and for survival in two LGs (6 and 9). The maximum
likelihood methodology identified QTL in three LGs (5, 6 and 9) for both traits.
Significant association between disease traits and genotypes was detected for
several markers, some of them explaining up to 17% of the phenotypic variance. We
also identified candidate genes located in the detected QTL using data from
previously mapped markers. CONCLUSIONS: Several regions controlling resistance to
A. salmonicida in turbot have been detected. The observed concordance between
different statistical methods at particular linkage groups gives consistency to
our results. The detected associated markers could be useful for genetic breeding
strategies. A finer mapping will be necessary at the detected QTL intervals to
narrow associations and around the closely associated markers to look for
candidate genes through comparative genomics or positional cloning strategies.
The identification of associated variants at specific genes will be essential,
together with the QTL associations detected in this study, for future marker
assisted selection programs.
PMID- 22047501
TI - Addressing the Grand Challenge of atmospheric carbon dioxide: geologic
sequestration vs. biological recycling.
AB - On February 15, 2008, the National Academy of Engineering unveiled their list of
14 Grand Challenges for Engineering. Building off of tremendous advancements in
the past century, these challenges were selected for their role in assuring a
sustainable existence for the rapidly increasing global community. It is no
accident that the first five Challenges on the list involve the development of
sustainable energy sources and management of environmental resources. While the
focus of this review is to address the single Grand Challenge of "develop carbon
sequestration methods", is will soon be clear that several other Challenges are
intrinsically tied to it through the principles of sustainability. How does the
realm of biological engineering play a role in addressing these Grand Challenges?
PMID- 22047502
TI - Re-examination of the dimerization state of leucine-rich repeat kinase 2:
predominance of the monomeric form.
AB - Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene have been identified
in PARK8, a major form of autosomal-dominantly inherited familial Parkinson's
disease, although the biochemical properties of LRRK2 are not fully understood.
It has been proposed that LRRK2 predominantly exists as a homodimer on the basis
of the observation that LRRK2, with a theoretical molecular mass of 280 kDa,
migrates at 600 kDa (p600 LRRK2) on native polyacrylamide gels. In the present
study, we biochemically re-examined the nature of p600 LRRK2 and found that p600
LRRK2 was fractionated with a single peak at ~272 kDa by ultracentrifugation on a
glycerol gradient. In addition, p600 LRRK2 behaved similarly to monomeric
proteins upon two-dimensional electrophoretic separation. These results suggested
a monomeric composition of p600 LRRK2 within cells. The p600 LRRK2 exhibited
kinase activity as well as GTP-binding activity, and forced dimerization of LRRK2
neither upregulated its kinase activity nor altered its subcellular localization.
Collectively, we conclude that the monomer form of LRRK2 is predominant within
cells, and that dimerization is dispensable for its enzymatic activity.
PMID- 22047503
TI - RNA interference-based resistance against a legume mastrevirus.
AB - BACKGROUND: RNA interference (RNAi) is a homology-dependant gene silencing
mechanism and has been widely used to engineer resistance in plants against RNA
viruses. However, its usefulness in delivering resistance against plant DNA
viruses belonging to family Geminiviridae is still being debated. Although the
RNAi approach has been shown, using a transient assay, to be useful in countering
monocotyledonous plant-infecting geminiviruses of the genus Mastrevirus, it has
yet to be investigated as a means of delivering resistance to dicot-infecting
mastreviruses. Chickpea chlorotic dwarf Pakistan virus (CpCDPKV) is a legume
infecting mastrevirus that affects chickpea and other leguminous crops in
Pakistan. RESULTS: Here a hairpin (hp)RNAi construct containing sequences
encompassing part of replication-associated protein gene, intergenic region and
part of the movement protein gene of CpCDPKV under the control of the Cauliflower
mosaic virus 35S promoter has been produced and stably transformed into Nicotiana
benthamiana. Plants harboring the hairpin construct were challenged with CpCDPKV.
All non-transgenic N. benthamiana plants developed symptoms of CpCDPKV infection
within two weeks post-inoculation. In contrast, none of the inoculated transgenic
plants showed symptoms of infection and no viral DNA could be detected by
Southern hybridization. A real-time quantitative PCR analysis identified very low
level accumulation of viral DNA in the inoculated transgenic plants. CONCLUSIONS:
The results presented show that the RNAi-based resistance strategy is useful in
protecting plants from a dicot-infecting mastrevirus. The very low levels of
virus detected in plant tissue of transgenic plants distal to the inoculation
site suggest that virus movement and/or viral replication was impaired leading to
plants that showed no discernible signs of virus infection.
PMID- 22047504
TI - Palladium-catalyzed allylic substitution with (eta6-arene-CH2Z)Cr(CO)(3)-based
nucleophiles.
AB - Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has
been intensively studied, there is a lack of general methods to employ simple
benzylic nucleophiles. Such a method would facilitate access to "alpha-2-propenyl
benzyl" motifs, which are common structural motifs in bioactive compounds and
natural products. We report herein the palladium-catalyzed allylation reaction of
toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of
cyclic and acyclic allylic electrophiles can be employed with in situ generated
(eta(6)-C(6)H(5)CHLiR)Cr(CO)(3) nucleophiles. Catalyst identification was
performed by high throughput experimentation (HTE) and led to the
Xantphos/palladium hit, which proved to be a general catalyst for this class of
reactions. In addition to eta(6)-toluene complexes, benzyl amine and ether
derivatives (eta(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), OR) are also viable
pronucleophiles, allowing C-C bond-formation alpha to heteroatoms with excellent
yields. Finally, a tandem allylic substitution/demetalation procedure is
described that affords the corresponding metal-free allylic substitution
products. This method will be a valuable complement to the existing arsenal of
nucleophiles with applications in allylic substitution reactions.
PMID- 22047505
TI - Public perspectives about pharmacogenetic testing and managing ancillary
findings.
AB - AIMS: Pharmacogenetic (PGx) tests are intended to improve therapeutic outcomes
through predicting a patient's likelihood to respond to or experience an adverse
effect from a specific treatment. In addition, PGx testing may also generate
ancillary, or incidental, disease information unrelated to the purpose for which
the test was ordered. To assess public attitudes toward PGx testing, ancillary
disease risk information and related clinical issues, we conducted a series of
focus groups. RESULTS: Forty-five individuals recruited from Durham, NC,
participated in four focus groups. Overall, participants were enthusiastic about
PGx testing, though expressed concerns about privacy, confidentiality, and
psychological harms associated with ancillary information. Focus group
participants believed that physicians had a responsibility to disclose ancillary
risk information, but were concerned about managing and coping with unexpected
disease risk information. CONCLUSION: We find that participants welcomed the
integration of PGx testing into therapeutic decision-making. Public concerns
about PGx testing and ancillary information specifically centered on personal
implications of learning such additional information, suggesting that patient
provider discussion of the benefits and risks of testing will be necessary until
public familiarity with these tests increases.
PMID- 22047506
TI - Association of CD36 gene variants and metabolic syndrome in Iranians.
AB - AIMS: The CD36 gene encodes for a membrane receptor that facilitates fatty-acid
uptake and utilization. Genetic variants of the CD36 gene have been associated
with metabolic syndrome (MetS). We aimed to evaluate the association between the
rs10499859A>G and rs13246513C>T polymorphisms and MetS components. METHODS: For
this case-control study, 140 MetS and 187 normal subjects were randomly selected
from the Tehran Lipid and Glucose Study participants. Biochemical and
anthropometrical variables were measured. Genotyping for both single nucleotide
polymorphisms (SNPs) was performed by polymerase chain reaction-restriction
fragment length polymorphism. RESULTS: Case and control groups were not different
in allele and genotype frequencies for these SNPs. However, the A and T alleles
of these SNPs were significantly associated with elevated levels of high-density
lipoprotein cholesterol (HDL-C) before age and sex adjustment (p=0.027 and 0.016,
respectively). Association between the A allele and body mass index (BMI) was
also significant after adjustment for MetS under the dominant model (p=0.009,
beta(2)=0.68). CONCLUSIONS: Based on our results, these polymorphisms do affect
HDL-C level and BMI (MetS components), although the effect may be slight and
restricted specifically to an environment-genotype.
PMID- 22047507
TI - Recurrent pregnancy loss and its relation to combined parental thrombophilic gene
mutations.
AB - BACKGROUND AND AIM: Recurrent pregnancy loss (RPL) is a heterogeneous disorder
that has been associated with antiphospholipid syndrome and other prothrombotic
parameters. We aimed to investigate the prevalence of 12 thrombophilic gene
mutations in RPL couples in the current results. METHOD: In a total of 543
Turkish women with RPL and 327 of their male partners (870 individuals with RPL),
and a control group of 106 fertile couples (control) were analyzed for factor V
leiden (FVL), factor V H1299R, factor II prothrombin G20210A, FXIII V34L, beta
fibrinogen -455G>A, plasminogen activator inhibitor-1 (PAI-1), GPIIIa L33P (HPA-1
a/b L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, ACE
I/D, Apo B R3500Q, and Apo E genes. RESULTS: The overall, heterozygous and/or
homozygous point mutations in FVL-FVR2, ApoE2, PAI-1, MTHFR C677T-A1298C, and ACE
genes were associated with RPL. There was no meaningful association between RPL
and other studied genes. CONCLUSION: The homozygosity of 4G in PAI-1 and MTHFR
C677T genes in women with RPL, and heterozygosity of FVL, FVR2, ACE, and ApoE2
genes in both parents play crucial role in RPL and should be considered as a risk
factor in RPL. Current results showed that RPL is related to combined parental
(not only maternal) thrombophilic gene mutations.
PMID- 22047508
TI - Does quality of care for hypertension in primary care vary with postcode area
deprivation? An observational study.
AB - BACKGROUND: Hypertension is a common major risk factor for stroke and coronary
heart disease. Little is known about how achievement of financially incentivised
and non-incentivised indicators of quality of care varies with deprivation, or
about the effect of financial incentives on health inequalities in hypertension.
General practices in the UK have received financial incentives for high quality
care since 2004. This study set out to assess the variations in achievement of
incentivised and non-incentivised quality indicators for hypertension by patient
area deprivation, before and after the introduction of financial incentives.
METHODS: Achievement of 14 quality indicators for hypertension in 304 patient
participants in 18 general practices in Norfolk, England was assessed one year
before (2003) and one year after (2005) the introduction of financial incentives.
Four indicators were incentivised and 10 were non-incentivised. Each
participant's postcode was linked to an index of multiple deprivation score.
RESULTS: The range of achievement of incentivised quality indicators was 65-94%
in the least deprived third of participants, and 77-94% in the most deprived
third in 2003 and 2005 combined. For non-incentivised indicators, the range was 7
85% in the least deprived and 24-93% in the most deprived third.Achievement of
incentivised quality indicators in 2003 and 2005 combined did not vary
significantly by area deprivation. Achievement of three of 10 non-incentivised
indicators was higher in participants from more deprived postcode areas:
providing lifestyle advice (odds ratio 1.34, 95% confidence interval 1.00-1.79),
assessment of peripheral vascular disease (1.54, 1.02-2.35) and
electrocardiography (1.38, 1.04-1.82). CONCLUSIONS: Participants from more
deprived areas received at least the same, and sometimes better, quality of care
than those from less deprived areas. Quality of care for hypertension in general
practice may not follow the inequitable distribution seen with some other
conditions.
PMID- 22047511
TI - ERRATUM.
PMID- 22047509
TI - Role of MetMAb (OA-5D5) in c-MET active lung malignancies.
AB - INTRODUCTION: MetMAb (OA-5D5) is a one-armed monoclonal antibody developed to
bind to and inhibit c-MET receptor tyrosine kinase. Though only in early clinical
testing, this agent holds great promise in diseases thought to be driven by c-MET
activation, as evidenced by the Phase II results in NSCLC where a benefit in
overall survival was observed in patients with MET-diagnostic-positive disease.
Thus far, both alone and in combination with other targeted agents, this drug has
been well tolerated and no new significant safety signals have been identified.
AREAS COVERED: This review summarizes the structure and function of the c-MET
receptor and its ligand hepatic growth factor (HGF), provides an overview of
select targeted monotherapies developed to interfere in the MET-HGF signaling
pathway, discusses pre-clinical and clinical data surrounding MetMAb, and
concludes with an expert opinion regarding this novel agent. EXPERT OPINION:
MetMAb has been well tolerated and based on Phase II data testing it, in
combination with erlotinib in advanced NSCLC, may have a role in improving
survival in patients with disease driven by c-MET activation. However, Phase III
validation is underway and the results of these studies will help elucidate which
patients will benefit most from this novel agent.
PMID- 22047516
TI - Interaction of biological molecules with clay minerals: a combined spectroscopic
and sorption study of lysozyme on saponite.
AB - The interaction of hen egg white lysozyme (HEWL) with Na- and Cs-exchanged
saponite was investigated using sorption, structural, and spectroscopic methods
as a model system to study clay-protein interactions. HEWL sorption to Na- and Cs
saponite was determined using the bicinchoninic acid (BCA) assay,
thermogravimetric analysis, and C and N analysis. For Na-saponite, the TGA and
elemental analysis-derived sorption maximum was 600 mg/g corresponding to a
surface coverage of 0.85 ng/mm(2) with HEWL occupying 526 m(2)/g based on a cross
sectional area of 13.5 nm(2)/molecule. HEWL sorption on Na-saponite was
accompanied by the release of 9.5 Na(+) ions for every molecule of HEWL sorbed
consistent with an ion exchange mechanism between the positively charged HEWL
(IEP 11) and the negatively charged saponite surface. The d-spacing of the HEWL
Na-saponite complex increased to a value of 4.4 nm consistent with the
crystallographic dimensions of HEWL of 3 * 3 * 4.5 nm. In the case of Cs
saponite, there was no evidence of interlayer sorption; however, sorption of HEWL
to the "external" surface of Cs-saponite showed a high affinity isotherm. FTIR
and Raman analysis of the amide I region of the HEWL-saponite films prepared from
water and D(2)O showed little perturbation to the secondary structure of the
protein. The overall hydrophilic nature of the HEWL-Na-saponite complex was
determined by water vapor sorption measurements. The clay retained its
hydrophilic character with a water content of 18% at high humidity corresponding
to 240 H(2)O molecules per molecule of HEWL.
PMID- 22047517
TI - Geographic variation in physicians' responses to a reimbursement change.
PMID- 22047518
TI - Evidence-based medicine in the EMR era.
PMID- 22047519
TI - The prevalence of undiagnosed chronic obstructive pulmonary disease in a primary
care population with respiratory tract infections - a case finding study.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an underdiagnosed
cause of morbidity and mortality worldwide. Prevalence of COPD has been shown to
be highly associated with positive smoking history and increasing age. Spirometry
is the method used for diagnosing COPD. However, identifying patients at risk of
COPD to undergo spirometry tests has been challenging. Therefore, there is a need
for new cost-effective and feasible diagnostic screening procedures for use in
primary care centers. Our aim was to describe the prevalence and severity of
undiagnosed COPD in a group of patients with respiratory infections attending
urgent primary care, and to identify those variables in patients' history that
could be used to detect the disease. METHODS: Patients of 40-75 years (n = 138)
attending urgent primary care center with acute respiratory tract infection,
positive smoking history and no previously known pulmonary disease underwent pre-
and post bronchodilator spirometry testing four to five weeks after the acute
infection. Prevalence and severity of COPD were estimated following the Global
Initiative for COPD (GOLD) criteria. Variables such as sex, age, current smoking
status, smoking intensity (pack years) and type of infection diagnosis were
assessed for possible associations with COPD. RESULTS: The prevalence of
previously undiagnosed COPD in our study group was 27%, of which 45% were in
stage 1 (FEV1 >= 80% of predicted), 53% in stage 2 (50 <= FEV1 < 80% of
predicted), 3% in stage 3 (30 <= FEV1 < 50% of predicted) and 0% in stage 4 (FEV1
< 30% of predicted). We found a significant association between COPD and age >=
55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack
years > 20) (OR = 3.2 [95% CI 1.2-8.5]). Sex, current smoking status and type of
infection diagnosis were not shown to be significantly associated with COPD.
CONCLUSION: A middle-aged or older patient with any type of common respiratory
tract infection, positive smoking history and no previously known pulmonary
disease has an increased likelihood of having underlying COPD. These patients
should be offered spirometry testing for diagnosis of COPD.
PMID- 22047520
TI - Positive association of the hepatic lipase gene polymorphism c.514C > T with
estrogen replacement therapy response.
AB - BACKGROUND: Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is
responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic
sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs).
The last polymorphism is the focus of the current study. The genotypes associated
with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous -
H), and TT (minor-allele homozygous - M). HL activity is significantly impaired
in individuals of the TT and CT genotypes. A total of 58 post-menopausal women
were studied. The subjects were hysterectomized women receiving hormone
replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a
day. The inclusion criteria were menopause of up to three years and normal blood
tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was
extracted from the buccal and blood cells of all 58 patients using a commercially
available kit (GFX(r) - Amersham-Pharmacia, USA). RESULTS: Statistically
significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in
total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This
group of good responders were carriers of the T allele; the CT and TT genotypes
were present significantly more frequently than in the group of non-responders (p
= 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t
= 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in
these patients. CONCLUSIONS: The variation in lipid profile associated with the C
514T polymorphism is significant, and the T allele is associated with the best
response to ERT.
PMID- 22047525
TI - Association between nitric oxide and 8-hydroxydeoxyguanosine levels in semen of
diabetic men.
AB - The incidence of diabetes mellitus is rapidly increasing in the world. One of the
complications of diabetes includes disturbance of the reproductive tract, such as
infertility, erectile dysfunction, and endocrine disruption. Nitric oxide (NO) is
a free radical produced by most cells including the human male and female
reproductive tracts. NO has a dual role where low concentrations are essential
for homeostatic cellular biology and physiology, but high levels have detrimental
effects relating to cellular damage from this reactive oxygen species (ROS). 8
hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside of DNA that is currently
used as a biomarker of cellular oxidative stress, where urinary levels can
correlate with diabetic nephropathy and retinopathy. Our aim was to investigate
the relationship between nitrate/nitrite levels and 8-OHdG levels in the semen of
diabetic and non-diabetic men. Concentrations of nitrate/nitrite and 8-OHdG were
examined in seminal plasma of 32 diabetic and 35 non-diabetic men. The level of
nitrate/nitrite was assayed by colorimetric reaction and 8-OHdG was measured by
ELISA. Our results showed that the seminal plasma nitrate/nitrite levels were
significantly higher in the diabetic group (p < 0. 01). There were also
significantly higher 8-OHdG levels in diabetic men compared to non-diabetic men
(p < 0.05). Regression analysis indicated that in diabetic men, nitrate/nitrite
levels correlated well with 8-OHdG levels (r = 0.64, p < 0.001). A significant
trend between nitrate/nitrite and sperm parameters was not observed. Our data
suggests that high levels of nitrate/nitrite in the semen of diabetic men is
suggestive of reactive oxygen species induced DNA damage that is correlated with
8-OHdG levels but not sperm parameters. These results support the further
investigation of NO and 8-OHdG as biomarkers for assessing male infertility.
PMID- 22047526
TI - Editorial.
PMID- 22047528
TI - Advancements in top-down proteomics.
PMID- 22047529
TI - Association between the results of the childhood asthma control test and
objective parameters in asthmatic children.
AB - OBJECTIVE: The Childhood Asthma Control Test (C-ACT), a seven-item, self
administered questionnaire, has been used as a tool to assess the control level
in children with asthma. The aim of this study was to determine whether the C-ACT
reflects airflow limitation and airway inflammation in addition to clinical
manifestations. METHODS: Asthmatic children aged 5-11 years who were able to
perform the lung function test and fractional exhaled nitric oxide (FeNO)
evaluation correctly were recruited during their regular visits. Children and
their parents were asked to answer the officially developed Japanese version of
the C-ACT. RESULTS: Among 258 children (176 boys, median age 9 years), there was
a significant positive correlation between the C-ACT score and the percent
predicted forced expiratory volume in 1 s (%FEV(1)) (r = 0.317, p < .001). The
accuracy of the C-ACT for identifying asthmatic subjects with normal lung
function (%FEV(1) >80%) described as the area under the receiver operating
characteristic curve was 71.5% (95% CI = 62.8-80.2%, p < .001), and based on the
Youden index the optimal cutoff score was 23 (sensitivity of 78% and specificity
of 54%). In contrast, there was no relationship between the C-ACT score and the
FeNO value. CONCLUSIONS: These results suggest that a cutoff score of 23 for the
C-ACT could be useful for identifying children with well-controlled asthma and
normal lung function. Further studies are warranted to develop an easy-to-use
questionnaire to assess the extent of airway inflammation in children.
PMID- 22047530
TI - Cationic liposome-mediated CXCR4 gene delivery into hematopoietic stem/progenitor
cells: implications for clinical transplantation and gene therapy.
AB - The chemokine stromal cell-derived factor (SDF)-1alpha/CXCL12 and its receptor
CXC chemokine receptor 4 (CXCR4) play a crucial role in the homing/engraftment
and retention of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow.
It has been shown using the viral gene transfer technique that CXCR4
overexpression on human CD34(+) HSPC significantly improves their engraftment in
murine models. However, clinical trials with gene therapy have revealed safety
concerns related to the immunogenicity of the viral carriers, due to the random
integration of viral genes into the host genome. Therefore, a method for CXCR4
gene delivery into HSPC that is safe, nonviral, and highly efficient is needed to
improve clinical transplantation and gene therapies. In this work, we
investigated the nonviral CXCR4 gene delivery into HSPC using the cationic
liposome agent IBAfect. We used CD34(+) cells from cord blood and the models of
immature hematopoietic cells expressing CD34 antigen, namely, leukemic cell lines
KG-1a and KG-1. Transfection efficiency was determined by flow cytometric
analysis 12, 24, 48, and 72 h after transfection, and the viability of cells
analyzed by trypan blue exclusion and MTS assays. The functional response of
CXCR4-transfected HSPC toward an SDF-1alpha gradient was determined by chemotaxis
assay. We found that ~25% transfection is achieved for KG-1a and KG-1 cells and
20% for HSPC, and that the viability of CXCR4-transfected HSPC is not
significantly altered. More importantly, overexpression of CXCR4 using IBAfect
significantly increased the chemotaxis of KG-1 cells and HSPC toward SDF-1alpha.
However, we tested 2 other commercially available cationic liposomes
(Lipofectamine 2000 and 1,2-dioleoyl-3-trimethylammonium-propane [DOTAP]) in
parallel, and we found that they failed to deliver the CXCR4 gene into cells
under the same conditions. These results suggest that IBAfect-mediated in vitro
gene delivery to overexpress CXCR4 on HSPC is a safe and efficient technique with
great potential for improving the efficacy of HSPC transplantation and gene
therapy protocols.
PMID- 22047531
TI - MicroRNA profiling of diverse endothelial cell types.
AB - BACKGROUND: MicroRNAs are ~22-nt long regulatory RNAs that serve as critical
modulators of post-transcriptional gene regulation. The diversity of miRNAs in
endothelial cells (ECs) and the relationship of this diversity to epithelial and
hematologic cells is unknown. We investigated the baseline miRNA signature of
human ECs cultured from the aorta (HAEC), coronary artery (HCEC), umbilical vein
(HUVEC), pulmonary artery (HPAEC), pulmonary microvasculature (HPMVEC), dermal
microvasculature (HDMVEC), and brain microvasculature (HBMVEC) to understand the
diversity of miRNA expression in ECs. RESULTS: We identified 166 expressed
miRNAs, of which 3 miRNAs (miR-99b, miR-20b and let-7b) differed significantly
between EC types and predicted EC clustering. We confirmed the significance of
these miRNAs by RT-PCR analysis and in a second data set by Sylamer analysis. We
found wide diversity of miRNAs between endothelial, epithelial and hematologic
cells with 99 miRNAs shared across cell types and 31 miRNAs unique to ECs. We
show polycistronic miRNA chromosomal clusters have common expression levels
within a given cell type. CONCLUSIONS: EC miRNA expression levels are generally
consistent across EC types. Three microRNAs were variable within the dataset
indicating potential regulatory changes that could impact on EC phenotypic
differences. MiRNA expression in endothelial, epithelial and hematologic cells
differentiate these cell types. This data establishes a valuable resource
characterizing the diverse miRNA signature of ECs.
PMID- 22047532
TI - Antioxidant activity of seagrasses of the Mandapam coast, India.
AB - CONTEXT: In the search for new sources of safe and inexpensive antioxidants, the
leaves of eight species of seagrasses were screened for antioxidant properties.
OBJECTIVE: Most of the seagrasses were evaluated for the first time for their
antioxidant activities. MATERIALS AND METHODS: Total phenolic content and in
vitro antioxidant activity using, 2,2-diphenyl-1-picrylhydrozyl (DPPH) radical
scavenging capacity and FRAP assay. RESULTS: The leaves of Halophila stipulacea
(Forssk.) Aschers showed high levels of phenols (1.398 +/- 0.055 mg GAE/g) and
high reducing power (46.289 +/- 1.002) in terms of mg GAE/g. Similarly, H.
pinifolia exhibited high total antioxidant activity (132.38, 75.027 mg AscAE/g)
and a high percentage of DPPH radical scavenging activity (68.14%). The TAA and
FRAP assays showed positive and significantly high correlation (R2 = 0.646). The
total phenolic content in the seagrass extracts showed a better correlation with
reducing power (R2 = 0.597) than the DPPH radical-scavenging activity (R2 =
0.495). DISCUSSION AND CONCLUSIONS: The antioxidant capacities of the seagrasses
showed potential rich sources of natural antioxidants. Further studies are
necessary for isolation and characterization of the active antioxidant compounds,
which can be used to treat various oxidative stress-related diseases.
PMID- 22047533
TI - Impact of the use of cryobank samples in a selected cattle breed: a simulation
study.
AB - BACKGROUND: High selection pressure on domestic cattle has led to an undesirable
increase in inbreeding, as well as to the deterioration of some functional traits
which are indirectly selected. Semen stored in a cryobank may be a useful way to
redirect selection or limit the loss of genetic diversity in a selected breed.
The purpose of this study was to analyse the efficiency of current cryobank
sampling methods, by investigating the benefits of using cryopreserved semen in a
selection scheme several generations after the semen was collected. METHODS: The
theoretical impact of using cryopreserved semen in a selection scheme of a dairy
cattle breed was investigated by simulating various scenarios involving two
negatively correlated traits and a change in genetic variability of the breed.
RESULTS: Our results indicate that using cryopreserved semen to redirect
selection will have an impact on negatively selected traits only if it is
combined with major changes in selection objectives or practices. If the purpose
is to increase genetic diversity in the breed, it can be a viable option.
CONCLUSIONS: Using cryopreserved semen to redirect selection or to improve
genetic diversity should be carried out with caution, by considering the pros and
cons of prospective changes in genetic diversity and the value of the selected
traits. However, the use of genomic information should lead to more interesting
perspectives to choose which animals to store in a cryobank and to increase the
value of cryobank collections for selected breeds.
PMID- 22047535
TI - Identifying and prioritizing strategies for comprehensive liver cancer control in
Asia.
AB - BACKGROUND: Liver cancer is both common and burdensome in Asia. Effective liver
cancer control, however, is hindered by a complex etiology and a lack of
coordination across clinical disciplines. We sought to identify strategies for
inclusion in a comprehensive liver cancer control for Asia and to compare
qualitative and quantitative methods for prioritization. METHODS: Qualitative
interviews (N = 20) with international liver cancer experts were used to identify
strategies using Interpretative Phenomenological Analysis and to formulate an
initial prioritization through frequency analysis. Conjoint analysis, a
quantitative stated-preference method, was then applied among Asian liver cancer
experts (N = 20) who completed 12 choice tasks that divided these strategies into
two mutually exclusive and exhaustive subsets. Respondents' preferred plan was
the primary outcome in a choice model, estimated using ordinary least squares
(OLS) and logistic regression. Priorities were then compared using Spearman's
Rho. RESULTS: Eleven strategies were identified: Access to treatments; Centers of
excellence; Clinical education; Measuring social burden; Monitoring of at-risk
populations; Multidisciplinary management; National guidelines; Public awareness;
Research infrastructure; Risk-assessment and referral; and Transplantation
infrastructure. Qualitative frequency analysis indicated that Risk-assessment and
referral (85%), National guidelines (80%) and Monitoring of at-risk populations
(80%) received the highest priority, while conjoint analysis pointed to
Monitoring of at-risk populations (p < 0.001), Centers of excellence (p = 0.002),
and Access to treatments (p = 0.004) as priorities, while Risk-assessment and
referral was the lowest priority (p = 0.645). We find moderate concordance
between the qualitative and quantitative methods (rho = 0.20), albeit
insignificant (p = 0.554), and a strong concordance between the OLS and logistic
regressions (rho = 0.979; p < 0.0001). CONCLUSIONS: Identified strategies can be
conceptualized as the ABCs of comprehensive liver cancer control as they focus on
Antecedents, Better care and Connections within a national strategy. Some
concordance was found between the qualitative and quantitative methods (e.g.
Monitoring of at-risk populations), but substantial differences were also
identified (e.g. qualitative methods gave highest priority to risk-assessment and
referral, but it was the lowest for the quantitative methods), which may be
attributed to differences between the methods and study populations, and
potential framing effects in choice tasks. Continued research will provide more
generalizable estimates of priorities and account for variation across
stakeholders and countries.
PMID- 22047536
TI - Synthesis and spectroscopic analysis of a stereoisomer library of the
phytophthora mating hormone alpha1 and derived bis-Mosher esters.
AB - Fluorous mixture synthesis provided all eight diastereomers of the phytophthora
hormone alpha1 with the R configuration at C11 as individual samples after
demixing and detagging. The library of all possible bis-Mosher esters (16) was
then made by esterification. Complete sets of (1)H, (13)C, and (for the Mosher
esters) (19)F NMR spectra were recorded, assigned, and compared with each other
and with published spectra. Not all of the spectra are unique, and the (1)H NMR
spectra of the Mosher esters provided the most information. The previous
assignment of the natural sample as an "all-R" stereoisomer mixed with its 3S
epimer was confirmed.
PMID- 22047537
TI - Associations between levels of serum perfluorinated chemicals and adiponectin in
a young hypertension cohort in Taiwan.
AB - In animals, perfluorinated chemicals (PFCs), specifically perfluorooctanoic acid
(PFOA) and perfluorooctane sulfate (PFOS), function as peroxisome proliferator
activated receptor (PPAR) alpha agonists. However, the relevance of animal
(primarily rodent) data to humans is unresolved. While plasma adiponectin level
is very responsive to PPAR gamma agonist drugs, it has not been determined
whether adiponectin level is related to serum PFCs concentrations. In the present
study, 287 subjects (12-30 years of age) were recruited to determine the
relationship between serum level of PFCs and serum level of adiponectin. The
results showed males had higher serum PFOS concentrations than females and that
those with metabolic syndrome had lower serum PFOA than controls. Besides, it
showed regional elevations of the perfluoroundecanoic acid (PFUA) (median
concentration: 7.11 ng/mL) in the study subjects. No relationship of PFOA, PFOS,
PFUA, and the sum of all four PFCs was found to glucose homeostasis, adiponectin
level, lipid profile, and inflammatory markers. The median and the range of
perfluorononanoic acid (PFNA) concentration (in ng/mL; for four categories
corresponding to the <50, 50-74, 75-89, and >=90th percentiles) were 0.38 (0.38
1.68), 3.22 (1.73-4.65), 5.85 (4.75-8.29), 10.56 (8.40-25.40), respectively.
After controlling for confounding factors, multiple linear regression analysis
revealed that the mean natural log-transformed level of adiponectin increased
significantly across categories of PFNA (in ng/mL; 8.78, 8.73, 9.06, 9.36; P for
trend = 0.010 in the full model). In conclusion, higher serum PFNA concentration
is associated with elevated serum adiponectin concentration.
PMID- 22047541
TI - Characteristics of epstein barr virus variants associated with gastric carcinoma
in Southern Tunisia.
AB - BACKGROUND: EBV-associated Gastric Carcinoma (EBVaGC) has a distinct clinical
features and its prevalence is variable worldwide. RESULTS: To determine the
prevalence of EBVaGC in Tunisia, EBV-encoded small RNA (EBER) expression was
assessed in 81 gastric carcinoma (GC) specimens. The nuclear EBER expression was
detected in 12 out of 81 GC cases (14.81%) and concordance between the score
range of EBER staining and the number of EBV DNA copies as estimate by QPCR is
observed. On the other hand, we found that EBVaGC strongly correlated with age at
diagnosis, and weakly with tumor differentiation and venous invasion.Furthermore,
the EBVaGC specimens were subjected to determine the EBV DNA polymorphisms. Our
results show a unique genetic profile of the EBV strains regarding the A and D
types, the F prototype, the retention of XhoI restriction site and the 30 bp del
LMP1 variant. According to our previous studies on nasopharyngeal carcinoma
(NPC), we suggested that EBV strains associated to GC and NPC shared some
similarities in Tunisian patients. CONCLUSION: The prevalence of EBVaGC is of
14.81% in the southern Tunisia and that common EBV strain are associated with
both NPC and GC which are likely to differ from Asian strains. Our findings
support therefore a certain geographical distribution of EBV strains which is not
restricted to EBV-associated malignancies.
PMID- 22047543
TI - Nonparametric combinatorial sequence models.
AB - This work considers biological sequences that exhibit combinatorial structures in
their composition: groups of positions of the aligned sequences are "linked" and
covary as one unit across sequences. If multiple such groups exist, complex
interactions can emerge between them. Sequences of this kind arise frequently in
biology but methodologies for analyzing them are still being developed. This
article presents a nonparametric prior on sequences which allows combinatorial
structures to emerge and which induces a posterior distribution over factorized
sequence representations. We carry out experiments on three biological sequence
families which indicate that combinatorial structures are indeed present and that
combinatorial sequence models can more succinctly describe them than simpler
mixture models. We conclude with an application to MHC binding prediction which
highlights the utility of the posterior distribution over sequence
representations induced by the prior. By integrating out the posterior, our
method compares favorably to leading binding predictors.
PMID- 22047542
TI - The VICI-trial: high frequency oscillation versus conventional mechanical
ventilation in newborns with congenital diaphragmatic hernia: an international
multicentre randomized controlled trial.
AB - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly
of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It
is associated with a high risk of mortality and pulmonary morbidity. Previous
retrospective studies have reported high frequency oscillatory ventilation (HFO)
to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to
be associated with worse outcome. We therefore aimed to develop a randomized
controlled trial to compare initial ventilatory treatment with high-frequency
oscillation and conventional ventilation in infants with CDH. METHODS/DESIGN:
This trial is designed as a multicentre trial in which 400 infants (200 in each
arm) will be included. Primary outcome measures are BPD, described as oxygen
dependency by day 28 according to the definition of Jobe and Bancalari, and/or
mortality by day 28. All liveborn infants with CDH born at a gestational age of
over 34 weeks and no other severe congenital anomalies are eligible for
inclusion. Parental informed consent is asked antenatally and the allocated
ventilation mode starts within two hours after birth. Laboratory samples of
blood, urine and tracheal aspirate are taken at the first day of life, day 3, day
7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung
injury and pulmonary hypertension. DISCUSSION: To date, randomized clinical
trials are lacking in the field of CDH. The VICI-trial, as the first randomized
clinical trial in the field of CDH, may provide further insight in ventilation
strategies in CDH patient. This may hopefully prevent mortality and morbidity.
TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1310.
PMID- 22047544
TI - The necessity for the coating of perfluorodecalin-filled poly(lactide-co
glycolide) microcapsules in the presence of physiological cholate concentrations:
Tetronic-908 as an exemplary polymeric surfactant.
AB - Recently, we demonstrated that biodegradable poly(lactide-co-glycolide) (PLGA)
micro- and nanocapsules with a liquid content of perfluorodecalin are principally
useful for the development of artificial oxygen carriers. In order to solve a
decisive and well-known problem with PLGA microcapsules, i.e. the spontaneous
agglomeration of the capsules after depletion of the emulsifying agent (i.e.
cholate), coating with the ABA block copolymer, Tetronic-908 was studied. After
Tetronic-908 treatment at concentrations that were harmless to cultured cells,
the clustering of the microcapsules was prevented, the adsorption of opsonins was
decreased and the attachment to cells was inhibited, but the oxygen transport
capacity of PLGA microcapsules was even increased. The present data clearly show
that perfluorodecalin-filled PLGA microcapsules must be coated before decreasing
the emulsifying agent cholate to physiological concentrations, in order to
develop a solution that has the capabilities to function as a potential
artificial oxygen carrier suspension.
PMID- 22047545
TI - Microencapsulation using vibrating technology.
AB - For over a half a century now, microencapsulation has played a very important
role in many industries and in the recent decades, this versatile technology has
been applied to numerous biotechnology and medical processes. However, successful
application in these areas requires a methodology which has the capability to
produce mono-dispersed, homogenous-shaped capsules, with a narrow size
distribution, using a short production time. The manufacture of capsules using
vibrating technology has gained significant interest mainly due to its simplistic
approach to produce homogenous microcapsules with the desired characteristics for
biotechnological and medical processes. However, certain limitations still exist
for this methodology, which include the inability to manufacture microcapsules at
large quantities and/or using highly viscous polymers. In this review, a detailed
description of the theoretical and practical aspects behind the production of
different types of alginate-based microcapsules, for application in
biotechnological and medical processes, using vibrating technology, is given.
PMID- 22047546
TI - Formulation, optimization and evaluation of spray-dried mucoadhesive microspheres
as intranasal carriers for Valsartan.
AB - This investigation deals with the intranasal delivery of Valsartan, encapsulated
in HPMC-based spray-dried mucoadhesive microspheres, with an aim to provide rapid
absorption and quick onset of action for treating hypertension. A 23-factorial
design has been employed for the assessment of influence of three independent
variables, namely inlet temperature, feed-flow rate and drug-polymer ratio on
production yield, particle size and in vitro drug diffusion of the prepared
microspheres. Microspheres were evaluated for particle size, entrapment
efficiency, swelling property, in vitro mucoadhesion, in vitro drug diffusion, ex
vivo drug permeation, histopathological examination and stability studies. The
results of differential scanning calorimetry, X-ray diffraction and scanning
electron microscopy revealed molecular dispersion of Valsartan into microspheres
with spherical shape and smooth surface. Optimized formulation indicated good
mucoadhesion with no severe sign of damage on nasal mucosa. Results of the non
invasive animal studies in dexamethasone-induced hypertensive rat model suggested
the suitability of investigated drug delivery system for intranasal
administration.
PMID- 22047547
TI - PEGylated estradiol benzoate liposomes as a potential local vascular delivery
system for treatment of restenosis.
AB - This study was directed towards the preparation and optimization of PEGylated
(PEG, poly(ethylene glycol)) estradiol benzoate (ESB)-loaded liposomes to be used
for the treatment of restenosis by local vascular delivery. Various liposomal
formulations were prepared by thin film hydration method followed by sonication.
Response surface methodology was applied to study the influence of three
different independent variables, on the response of entrapment efficiency (%EE).
Liposomes were characterized in terms of size, zeta potential, %EE and release
profile. Incorporation of ESB was higher in egg phosphatidylcholine (EPC)
liposomes, whereas the drug was displaced from liposomes, as the cholesterol
(Chol) content of liposome increased. The optimum formulation composed of
EPC/dioleyloxy trimethylammonium propane/distearoylphosphatidylethanolamine
PEG2000 with a molar proportion of 8.5:1:0.5 had the highest EE. In vivo studies
in the balloon-injured rat carotid arteries revealed the potential of ESB-loaded
liposomes as efficient local and controlled drug delivery systems to reduce
restenosis.
PMID- 22047548
TI - Mixture designs in the optimisation of PLGA nanoparticles: influence of organic
phase composition on beta-aescin encapsulation.
AB - The objective of this study was to enhance the encapsulation of the
antileishmanial saponin aescin in poly(D,L-lactide-co-glycolide) (PLGA)
nanoparticles (NPs). We prepared the NPs by the O/W and W/O/W combined
emulsification solvent evaporation/salting-out technique and investigated the
influence of organic phase composition on the NPs' size, zeta potential and
entrapment efficiency (EE%) using mixture designs. The obtained NPs were
monodispersed with Z(ave)<300 nm and exhibited negative zeta potentials. For the
single emulsion, the co-solvent concentration was shown to be the primary
determinant of drug entrapment. The EE% increased from 14% to 22% by decreasing
the amount of DMSO from 80% to 25% (v/v) in the organic polymer solution. For the
double emulsion, EE% was 22% on average and independent of the organic phase
composition. The double-emulsion technique did not enhance the aescin
encapsulation as expected due to its amphiphilic nature. The optimised aescin
loaded NPs meet the requirements for further in vitro activity tests.
PMID- 22047549
TI - Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in
vitro, pharmacokinetic and pharmacodynamic investigations.
AB - A multiple-unit system comprising mucoadhesive bilayer buccal tablets of
carvedilol-loaded chitosan microspheres (CMs) was developed to improve
bioavailability and therapeutic efficacy of carvedilol. Drug-loaded CMs were
prepared by spray drying, evaluated for powder and particle characteristics, and
optimized batch of CMs was compressed into bilayer buccal tablets using Carbopol.
Tablets were evaluated for physicochemical parameters, in vitro drug release, in
vivo pharmacokinetic and pharmacodynamic studies. Optimized formulation, CMT1
(CMT, chitosan microsphere tablet) showed maximum mucoadhesive force (50 +/- 1.84
dyne/cm2), exhibited 73.08 +/- 3.05% drug release and demonstrated zero-order
kinetics with non-Fickian release mechanism. Pharmacokinetic studies in rabbits
showed significantly higher C(max) (71.26 +/- 6.45 ng/mL), AUC(0-10) (AUC, area
under the curve 390.75 +/- 5.23 ng/mL/h) and AUC(0-infinity) (664.72 ng/mL/h)
than carvedilol oral tablet. Pharmacodynamic studies confirmed reduction in mean
arterial pressure, heart rate, body weight and triglyceride on administration of
bilayer buccal tablet compared to oral carvedilol tablet. Multiple-unit system
exhibited enhanced bioavailability and sustained release of carvedilol,
indicating its improved therapeutic potential for the treatment of hypertension.
PMID- 22047550
TI - Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal
tumor: a rare adverse event.
AB - BACKGROUND: Imatinib mesylate has been the standard therapeutic treatment for
chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor
(GIST). It is well tolerated with mild adverse effects. Gynecomastia development
during the course of treatment has been rarely reported. METHODS: Ninety-eight
patients with advanced or recurrent GIST were treated with imatinib mesylate.
Among the fifty-seven male patients six developed gynecomastia during the
treatment. The lesions were confirmed by sonography. Sex hormone levels were
determined in six patients with and without the presence of gynecomastia
respectively. The patients with gynecomatia were treated with tamoxifene and the
sex hormones were assayed before and after tamoxifene treatment. RESULTS: In
patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5
centimeters in diameter. Their serum free testosterone levels ranged between
356.61 and 574.60 ng/dl with a mean +/- SD of 408.64 +/- 82.06 ng/dl (95% CI
343.03~474.25 ng/dl), which is within the normal range. The level of serum
estradiol was 42.89 +/- 16.54 pg/ml (95% CI 29.66~56.12 pg/ml). Three patients
had higher levels (43.79~71.21 pg/ml) and the others' were within normal range of
27.00~34.91 pg/ml. Six patients without the development of gynecomastia had
normal free testosterone. One patient died because of large tumor burden. The sex
hormones had no significant changes before and after tamoxifene treatment.(P >
0.05) CONCLUSIONS: Testosterone levels were not decreased in the six GIST
patients with gynecomastia. Three patients had increased serum estradiol level
which suggests that imbalance of sex hormones may be the cause of gynecomastia
during treatment with imatinib mesylate.
PMID- 22047551
TI - Drug-loaded and superparamagnetic iron oxide nanoparticle surface-embedded
amphiphilic block copolymer micelles for integrated chemotherapeutic drug
delivery and MR imaging.
AB - We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic
block copolymers physically encapsulated with hydrophobic drugs within micellar
cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles
within hydrophilic coronas, which possess integrated functions of
chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast
enhancement. Poly(epsilon-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b
PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at
first by combining ring-opening polymerization (ROP), atom transfer radical
polymerization (ATRP), and post- modification techniques, where OEGMA and FA are
oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing
moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX),
and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic
coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b
P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of
micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms
at the surface of SPIO nanoparticles. The controlled and sustained release of PTX
from hybrid micelles was achieved, exhibiting a cumulative release of ~61%
encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of
surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe),
the clustering of SPIO nanoparticles within micellar coronas led to considerably
enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid
micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved
performance. Moreover, preliminary experiments of in vivo MR imaging were also
conducted. These results indicate that amphiphilic block copolymer micelles
surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a
new generation of nanoplatform integrating targeted drug delivery, controlled
release, and disease diagnostic functions.
PMID- 22047552
TI - Insight into cross-talk between intra-amoebal pathogens.
AB - BACKGROUND: Amoebae are phagocytic protists where genetic exchanges might take
place between amoeba-resistant bacteria. These amoebal pathogens are able to
escape the phagocytic behaviour of their host. They belong to different bacterial
phyla and often show a larger genome size than human-infecting pathogens. This
characteristic is proposed to be the result of frequent gene exchanges with other
bacteria that share a sympatric lifestyle and contrasts with the genome reduction
observed among strict human pathogens. RESULTS: We sequenced the genome of a new
amoebal pathogen, Legionella drancourtii, and compared its gene content to that
of a Chlamydia-related bacterium, Parachlamydia acanthamoebae. Phylogenetic
reconstructions identified seven potential horizontal gene transfers (HGTs)
between the two amoeba-resistant bacteria, including a complete operon of four
genes that encodes an ABC-type transporter. These comparisons pinpointed
potential cases of gene exchange between P. acanthamoebae and Legionella
pneumophila, as well as gene exchanges between other members of the Legionellales
and Chlamydiales orders. Moreover, nine cases represent possible HGTs between
representatives from the Legionellales or Chlamydiales and members of the
Rickettsiales order. CONCLUSIONS: This study identifies numerous gene exchanges
between intracellular Legionellales and Chlamydiales bacteria, which could
preferentially occur within common inclusions in their amoebal hosts. Therefore
it contributes to improve our knowledge on the intra-amoebal gene properties
associated to their specific lifestyle.
PMID- 22047555
TI - Oxidative stress and leaf senescence.
AB - BACKGROUND: Senescence is an important developmental process that leads to the
cell death through highly regulated genetically controlled processes in plants.
Biotic and abiotic Oxidative stresses can also artificially induce senescence and
increase the production of reactive oxygen species (ROS) specifically in
chloroplast. One of the important oxidative stresses is paraquat that induces
deviation of electron from photosynthesis electron chain and lead to the
production of more ROS in chloroplast. Plants have evolved special adoptive
mechanism to reallocate nutrient to reproductive and juvenile organs in
senescence and different oxidative stresses. Rubisco seems to be the most
abundant protein in plants and is involved in many changes during senescence.
RESULTS: In the present study, the effects of ROS on Rubisco during senescence
and oxidative stresses were evaluated by measuring photosynthesis factors such as
net photosynthesis rate (Pn), stomatal conductance (G), evaporation rate (E),
intra cellular CO2 concentration (Ci), fluorescence and total protein during
three stages of development. Our results showed that in paraquat treated plants,
CO2 assimilation is the most effective factor that refers to Rubisco damages. The
highest correlation and regression coefficient belonged to Ci, while correlation
coefficient between photosynthesis rate and total protein was much smaller.
CONCLUSION: It appears in the early stage of oxidative stresses such as exposing
to paraquat, ROS has the most effect on Rubisco activity that induces more
susceptibility to Rubisco specific protease. Moreover, Rubisco deactivation acts
as an initiative signal for Rubisco degradation.
PMID- 22047554
TI - Temperature dependence of the heat diffusivity of proteins.
AB - In a combined experimental-theoretical study, we investigated the transport of
vibrational energy from the surrounding solvent into the interior of a heme
protein, the sperm whale myoglobin double mutant L29W-S108L, and its dependence
on temperature from 20 to 70 K. The hindered libration of a CO molecule that is
not covalently bound to any part of the protein but is trapped in one of its
binding pockets (the Xe4 pocket) was used as the local thermometer. Energy was
deposited into the solvent by IR excitation. Experimentally, the energy transfer
rate increased from (30 ps)(-1) at 20 K to (8 ps)(-1) at 70 K. This temperature
trend is opposite to what is expected, assuming that the mechanism of heat
transport is similar to that in glasses. In order to elucidate the mechanism and
its temperature dependence, nonequilibrium molecular dynamics (MD) simulations
were performed, which, however, predicted an essentially temperature-independent
rate of vibrational energy flow. We tentatively conclude that the MD potentials
overestimate the coupling between the protein and the CO molecule, which appears
to be the rate-limiting step in the real system at low temperatures. Assuming
that this coupling is anharmonic in nature, the observed temperature trend can
readily be explained.
PMID- 22047556
TI - Toward the definition of stereochemical requirements for MT2-selective
antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin
derivatives.
AB - New derivatives of 4-phenyl-2-propionamidotetralin (4-P-PDOT) were prepared and
tested on cloned MT1 and MT2 receptors, with the purpose of merging previously
reported pharmacophores for nonselective agonists and for MT2-selective
antagonists. A 8-methoxy group increases binding affinity of both (+/-)-cis- and
(+/-)-trans-4-P-PDOT, and it can be bioisosterically replaced by a bromine.
Conformational analysis of 8-methoxy-4-P-PDOT by molecular dynamics, supported by
NMR data, revealed an energetically favored conformation for the (2S,4S)-cis
isomer and a less favorable conformation for the (2R,4S)-trans one, fulfilling
the requirements of a pharmacophore model for nonselective melatonin receptor
agonists. A new superposition model, including features characteristic of MT2
selective antagonists, suggests that MT1/MT2 agonists and MT2 antagonists can
share the same arrangement for their pharmacophoric elements. The model correctly
predicted the eutomers of (+/-)-cis- and (+/-)-trans-4-P-PDOT. The model was
validated by preparing three dihydronaphthalene derivatives, either able or not
able to reproduce the putative active conformation of 4-P-PDOT.
PMID- 22047558
TI - Inducible apoptosis as a safety switch for adoptive cell therapy.
AB - BACKGROUND: Cellular therapies could play a role in cancer treatment and
regenerative medicine if it were possible to quickly eliminate the infused cells
in case of adverse events. We devised an inducible T-cell safety switch that is
based on the fusion of human caspase 9 to a modified human FK-binding protein,
allowing conditional dimerization. When exposed to a synthetic dimerizing drug,
the inducible caspase 9 (iCasp9) becomes activated and leads to the rapid death
of cells expressing this construct. METHODS: We tested the activity of our safety
switch by introducing the gene into donor T cells given to enhance immune
reconstitution in recipients of haploidentical stem-cell transplants. Patients
received AP1903, an otherwise bioinert small-molecule dimerizing drug, if graft
versus-host disease (GVHD) developed. We measured the effects of AP1903 on GVHD
and on the function and persistence of the cells containing the iCasp9 safety
switch. RESULTS: Five patients between the ages of 3 and 17 years who had
undergone stem-cell transplantation for relapsed acute leukemia were treated with
the genetically modified T cells. The cells were detected in peripheral blood
from all five patients and increased in number over time, despite their
constitutive transgene expression. A single dose of dimerizing drug, given to
four patients in whom GVHD developed, eliminated more than 90% of the modified T
cells within 30 minutes after administration and ended the GVHD without
recurrence. CONCLUSIONS: The iCasp9 cell-suicide system may increase the safety
of cellular therapies and expand their clinical applications. (Funded by the
National Heart, Lung, and Blood Institute and the National Cancer Institute;
ClinicalTrials.gov number, NCT00710892.).
PMID- 22047559
TI - Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors.
AB - BACKGROUND: Patients with severe hemophilia A and factor VIII inhibitors are at
increased risk for serious bleeding complications and progression to end-stage
joint disease. Effective strategies to prevent bleeding in such patients have not
yet been established. METHODS: We enrolled patients with hemophilia A who were
older than 2 years of age, had high-titer inhibitors, and used concentrates known
as bypassing agents for bleeding in a prospective, randomized, crossover study
comparing 6 months of anti-inhibitor coagulant complex (AICC), infused
prophylactically at a target dose of 85 U per kilogram of body weight (+/-15%) on
3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a
target dose of 85 U per kilogram [+/-15%] used for bleeding episodes). The two
treatment periods were separated by a 3-month washout period, during which
patients received on-demand therapy for bleeding. The primary outcome was the
number of bleeding episodes during each 6-month treatment period. RESULTS: Thirty
four patients underwent randomization; 26 patients completed both treatment
periods and could be evaluated per protocol for the efficacy analysis. As
compared with on-demand therapy, prophylaxis was associated with a 62% reduction
in all bleeding episodes (P<0.001), a 61% reduction in hemarthroses (P<0.001),
and a 72% reduction in target-joint bleeding (>=3 hemarthroses in a single joint
during a 6-month treatment period) (P<0.001). Thirty-three randomly assigned
patients received at least one infusion of the study drug and were evaluated for
safety. One patient had an allergic reaction to the study drug. CONCLUSIONS: AICC
prophylaxis at the dosage evaluated significantly and safely decreased the
frequency of joint and other bleeding events in patients with severe hemophilia A
and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA
ClinicalTrials.gov number, NCT00221195.).
PMID- 22047557
TI - A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
AB - BACKGROUND: Increasing the activity of defective cystic fibrosis transmembrane
conductance regulator (CFTR) protein is a potential treatment for cystic
fibrosis. METHODS: We conducted a randomized, double-blind, placebo-controlled
trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of
age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects
were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84
subjects, of whom 83 received at least one dose) or placebo (83, of whom 78
received at least one dose) for 48 weeks. The primary end point was the estimated
mean change from baseline through week 24 in the percent of predicted forced
expiratory volume in 1 second (FEV(1)). RESULTS: The change from baseline through
week 24 in the percent of predicted FEV(1) was greater by 10.6 percentage points
in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary
function were noted by 2 weeks, and a significant treatment effect was maintained
through week 48. Subjects receiving ivacaftor were 55% less likely to have a
pulmonary exacerbation than were patients receiving placebo, through week 48
(P<0.001). In addition, through week 48, subjects in the ivacaftor group scored
8.6 points higher than did subjects in the placebo group on the respiratory
symptoms domain of the Cystic Fibrosis Questionnaire-revised instrument (a 100
point scale, with higher numbers indicating a lower effect of symptoms on the
patient's quality of life) (P<0.001). By 48 weeks, patients treated with
ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving
placebo (P<0.001). The change from baseline through week 48 in the concentration
of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with
placebo was -48.1 mmol per liter (P<0.001). The incidence of adverse events was
similar with ivacaftor and placebo, with a lower proportion of serious adverse
events with ivacaftor than with placebo (24% vs. 42%). CONCLUSIONS: Ivacaftor was
associated with improvements in lung function at 2 weeks that were sustained
through 48 weeks. Substantial improvements were also observed in the risk of
pulmonary exacerbations, patient-reported respiratory symptoms, weight, and
concentration of sweat chloride. (Funded by Vertex Pharmaceuticals and others;
VX08-770-102 ClinicalTrials.gov number, NCT00909532.).
PMID- 22047560
TI - Host and pathogen factors for Clostridium difficile infection and colonization.
AB - BACKGROUND: Clostridium difficile infection is the leading cause of health care
associated diarrhea, and the bacterium can also be carried asymptomatically. The
objective of this study was to identify host and bacterial factors associated
with health care-associated acquisition of C. difficile infection and
colonization. METHODS: We conducted a 15-month prospective study in six Canadian
hospitals in Quebec and Ontario. Demographic information, known risk factors,
potential confounding factors, and weekly stool samples or rectal swabs were
collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile
isolates to determine the genotype. Levels of serum antibodies against C.
difficile toxins A and B were measured. RESULTS: A total of 4143 patients were
included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C.
difficile infection and colonization, respectively. Older age and use of
antibiotics and proton-pump inhibitors were significantly associated with health
care-associated C. difficile infection. Hospitalization in the previous 2 months;
use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies
against toxin B were associated with health care-associated C. difficile
colonization. Among patients with health care-associated C. difficile infection
and those with colonization, 62.7% and 36.1%, respectively, had the North
American PFGE type 1 (NAP1) strain. CONCLUSIONS: In this study, health care
associated C. difficile infection and colonization were differentially associated
with defined host and pathogen variables. The NAP1 strain was predominant among
patients with C. difficile infection, whereas asymptomatic patients were more
likely to be colonized with other strains. (Funded by the Consortium de Recherche
sur le Clostridium difficile.).
PMID- 22047561
TI - Results of the Medicare Health Support disease-management pilot program.
AB - BACKGROUND: In the Medicare Modernization Act of 2003, Congress required the
Centers for Medicare and Medicaid Services to test the commercial disease
management model in the Medicare fee-for-service program. METHODS: The Medicare
Health Support Pilot Program was a large, randomized study of eight commercial
programs for disease management that used nurse-based call centers. We randomly
assigned patients with heart failure, diabetes, or both to the intervention or to
usual care (control) and compared them with the use of a difference-in
differences method to evaluate the effects of the commercial programs on the
quality of clinical care, acute care utilization, and Medicare expenditures for
Medicare fee-for-service beneficiaries. RESULTS: The study included 242,417
patients (163,107 in the intervention group and 79,310 in the control group). The
eight commercial disease-management programs did not reduce hospital admissions
or emergency room visits, as compared with usual care. We observed only 14
significant improvements in process-of-care measures out of 40 comparisons. These
modest improvements came at substantial cost to the Medicare program in fees paid
to the disease-management companies ($400 million), with no demonstrable savings
in Medicare expenditures. CONCLUSIONS: In this large study, commercial disease
management programs using nurse-based call centers achieved only modest
improvements in quality-of-care measures, with no demonstrable reduction in the
utilization of acute care or the costs of care.
PMID- 22047562
TI - Ulcerative colitis.
PMID- 22047563
TI - Images in clinical medicine. Lingual zoster.
PMID- 22047564
TI - Clinical problem-solving. A bird's-eye view of fever.
PMID- 22047565
TI - Therapy for cystic fibrosis--the end of the beginning?
PMID- 22047566
TI - Eliminating cells gone astray.
PMID- 22047567
TI - Calcium handling in the failing heart and SUMO--weighing the evidence.
PMID- 22047569
TI - Wnt signaling and Dupuytren's disease.
PMID- 22047571
TI - CYP24A1 mutations in idiopathic infantile hypercalcemia.
PMID- 22047572
TI - CYP24A1 mutations in idiopathic infantile hypercalcemia.
PMID- 22047574
TI - Constrictive bronchiolitis in soldiers.
PMID- 22047575
TI - Constrictive bronchiolitis in soldiers.
PMID- 22047576
TI - Constrictive bronchiolitis in soldiers.
PMID- 22047578
TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes.
PMID- 22047579
TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes.
PMID- 22047580
TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes.
PMID- 22047581
TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes.
PMID- 22047582
TI - Hemophilia A induced by ipilimumab.
PMID- 22047584
TI - Images in clinical medicine. Metastasis of renal-cell carcinoma.
PMID- 22047590
TI - Measuring sexual function in community surveys: development of a conceptual
framework.
AB - Among the many psychometric measures of sexual (dys)function, none is entirely
suited to use in community surveys. Faced with the need to include a brief and
non-intrusive measure of sexual function in a general population survey, a new
measure was developed. Findings from qualitative research with men and women in
the community designed to inform the conceptual framework for this measure are
presented. Thirty-two semi-structured interviews with individuals recruited from
a general practice, an HIV/AIDS charity, and a sexual problems clinic were
conducted. From their accounts, 31 potential criteria of a functional sex life
were identified. Using evidence from qualitative data and the existing
literature, and applying a set of decision rules, the list was reduced to 13
(eight for those not in a relationship), and a further eight criteria were added
to enable individuals to self-rate their level of function and indicate the
severity of difficulties. These criteria constitute a conceptual framework that
is grounded in participant perceptions; is relevant to all, regardless of sexual
experience or orientation; provides opportunity to state the degree of associated
distress; and incorporates relational, psychological, and physiological aspects.
It provides the conceptual basis for a concise and acceptable measure of sexual
function.
PMID- 22047591
TI - Searching for phenotypic causal networks involving complex traits: an application
to European quail.
AB - BACKGROUND: Structural equation models (SEM) are used to model multiple traits
and the casual links among them. The number of different causal structures that
can be used to fit a SEM is typically very large, even when only a few traits are
studied. In recent applications of SEM in quantitative genetics mixed model
settings, causal structures were pre-selected based on prior beliefs alone.
Alternatively, there are algorithms that search for structures that are
compatible with the joint distribution of the data. However, such a search cannot
be performed directly on the joint distribution of the phenotypes since causal
relationships are possibly masked by genetic covariances. In this context, the
application of the Inductive Causation (IC) algorithm to the joint distribution
of phenotypes conditional to unobservable genetic effects has been proposed.
METHODS: Here, we applied this approach to five traits in European quail: birth
weight (BW), weight at 35 days of age (W35), age at first egg (AFE), average egg
weight from 77 to 110 days of age (AEW), and number of eggs laid in the same
period (NE). We have focused the discussion on the challenges and difficulties
resulting from applying this method to field data. Statistical decisions
regarding partial correlations were based on different Highest Posterior Density
(HPD) interval contents and models based on the selected causal structures were
compared using the Deviance Information Criterion (DIC). In addition, we used
temporal information to perform additional edge orienting, overriding the
algorithm output when necessary. RESULTS: As a result, the final causal structure
consisted of two separated substructures: BW->AEW and W35->AFE->NE, where an
arrow represents a direct effect. Comparison between a SEM with the selected
structure and a Multiple Trait Animal Model using DIC indicated that the SEM is
more plausible. CONCLUSIONS: Coupling prior knowledge with the output provided by
the IC algorithm allowed further learning regarding phenotypic causal structures
when compared to standard mixed effects SEM applications.
PMID- 22047592
TI - alpha7 Nicotinic receptor modulators for cognitive deficits in schizophrenia and
Alzheimer's disease.
AB - INTRODUCTION: Nicotinic receptors (nAChR), a class of ligand-gated ion channels,
are attractive targets in a variety of CNS diseases. The low-affinity alpha7
nAChR modulate the levels of various neurotransmitters, their receptor density is
affected in schizophrenia and a single nucleotide polymorphism in the promoter
region has been associated with higher risk for schizophrenia. AREAS COVERED:
This article reviews the scientific rationale for alpha7 nAChR stimulation and
presents a selection of alpha7-positive modulators that are in development for
cognitive deficits, both in Alzheimer's disease and in cognitive impairment
associated with schizophrenia. The available clinical information is reviewed and
the translational difficulties are discussed. EXPERT OPINION: In contrast to
preclinical models, clinical proof-of-concept studies so far have not shown clear
unequivocal cognitive benefit, although there are signs of clinical efficacy on
specific cognitive scales and on negative symptoms. Possible problems associated
with the clinical development include the impact of dosage and dosing schedule on
the balance between activation and desensitization of the ion channel, the
selection of comedication, robust human target engagement data and the choice of
clinical readout scales. A better understanding of the human biology of alpha7
nAChR is essential for improving the successful clinical development of this
promising target.
PMID- 22047593
TI - Contribution of spin and anisotropy to single molecule magnet behavior in a
family of bell-shaped Mn11Ln2 coordination clusters.
AB - The synthesis, structures, and magnetic properties of a family of isostructural
"bell-shaped" heterometallic coordination clusters
[Mn(III)(9)Mn(II)(2)La(III)(2)(MU(4)-O)(7)(MU(3)-O)(MU(3)
OH)(2)(piv)(10.8)(O(2)CC(4)H(3)O)(6.2)(NO(3))(2)(OH(2))(1.5)(MeCN)(0.5)].12CH(3)C
.2H(2)O (1) and [Mn(III)(9)Mn(II)(2)Ln(2)(MU(4)-O)(7)(MU (3)-O)(MU(3)
OH)(2)(piv)(10.6)(O(2)CC(4)H(3)O)(6.4)(NO(3))(2)(OH(2))].nCH(3)CN.H(2)O (Ln =
Pr(III), n = 8 (2); Ln = Nd(III), n = 10 (3); Ln = Eu(III), n = 17 (4); Ln =
Gd(III), n = 13 (5); piv = pivalate) are reported. The complexes were obtained
from the reaction of [Mn(III)(2)Mn(II)(4)O(2)(piv)(10)(4-Me-py)(2.5)(pivH)(1.5)]
and Ln(NO(3))(3).6H(2)O in the presence of 2-furan-carboxylic acid
(C(4)H(3)OCOOH) in CH(3)CN. Compounds 1-5 are isomorphous, crystallizing in the
triclinic space group P1 with Z = 2. The Mn(III) and Mn(II) centers together form
the shell of the bell, while the two Ln(III) centers can be regarded as the
bell's clapper. The magnetic properties of 1-4 reveal dominant antiferromagnetic
interactions between the magnetic centers leading to small spin ground states;
while those of 5 indicate similar antiferromagnetic interactions between the
manganese ions but with unusually strong ferromagnetic interactions between the
Gd(III) ions leading to a large overall spin ground state of S = 11-12. While ac
and dc magnetic measurements confirmed that Mn(11)Gd(2) (5) is a single-molecule
magnet (SMM) showing hysteresis loops at low temperatures, compounds 1-4 do not
show any slow relaxation of the magnetization, indicating that the S = 7 spin of
the ferromagnetic Gd(2) unit in 5 is a necessary contribution to its SMM
behavior.
PMID- 22047594
TI - Ertapenem for treatment of osteomyelitis: a case series.
AB - BACKGROUND: Ertapenem is a once-daily broad spectrum carbapenem that is
increasingly used to treat polymicrobial osteomyelitis due to diabetic foot and
traumatic wound infections. However, limited data exists on ertapenem use for
osteomyelitis. This study aimed to characterize outcomes and adverse effects with
empiric use of ertapenem for osteomyelitis. FINDINGS: A total of 112 patients
presenting to Duke, Durham Regional or Durham VA Medical Centers with a suspected
diagnosis of osteomyelitis and ertapenem use from 11/2001 to 8/2009 were
screened, and 12 subjects met inclusion criteria for the study. Mean age was 60
+/- 16 years, 68% were female, 75% were Caucasian, and the most common
comorbidities included diabetes (58%), peripheral vascular disease (42%), and
history of tobacco use (75%). Over half of the patients presented to a primary
care clinic or emergency room greater than six months after the onset of clinical
symptoms. Bone culture was obtained for diagnostic guidance in only two cases;
and surgical intervention was pursued in three cases. Patients received a mean
duration of 34.6 +/- 7.8 days of therapy, and in three cases, subsequent
suppressive oral antibiotics were given. Six (50%) patients met criteria for
clinical success, defined as resolution of clinical signs and symptoms of
infection such that discontinuation of antibiotics was deemed appropriate at end
of ertapenem therapy, without recurrence at one year follow-up. No adverse drug
effects were noted. CONCLUSIONS: In this case series of mostly community
acquired, lower extremity osteomyelitis, bone biopsy was infrequent, and an
average six-week course of empiric ertapenem was well-tolerated with curative
rates of 50% at one year.
PMID- 22047595
TI - A multidisciplinary survey on controversies in the use of EUS-guided FNA:
assessing perspectives of surgeons, oncologists and gastroenterologists.
AB - BACKGROUND: EUS-guided FNA can help diagnose and differentiate between various
pancreatic and other lesions.The aim of this study was to compare approaches
among involved/relevant physicians to the controversies surrounding the use of
FNA in EUS. METHODS: A five-case survey was developed, piloted, and validated. It
was collected from a total of 101 physicians, who were all either
gastroenterologists (GIs), surgeons or oncologists. The survey compared the
management strategies chosen by members of these relevant disciplines regarding
EUS-guided FNA. RESULTS: For CT operable T2NOM0 pancreatic tumors the research
demonstrated variance as to whether to undertake EUS-guided FNA, at p < 0.05. For
inoperable pancreatic tumors 66.7% of oncologists, 62.2% of surgeons and 79.1% of
GIs opted for FNA (p < 0.05). For cystic pancreatic lesions, oncologists were
more likely to send patients to surgery without FNA. For stable simple pancreatic
cysts (23 mm), most physicians (66.67%) did not recommend FNA. For a submucosal
gastric 19 mm lesion, 63.2% of surgeons recommended FNA, vs. 90.0% of oncologists
(p < 0.05). CONCLUSIONS: Controversies as to ideal application of EUS-FNA
persist. Optimal guidelines should reflect the needs and concerns of the
multidisciplinary team who treat patients who need EUS-FNA. Multi-specialty
meetings assembled to manage patients with these disorders may be enlightening
and may help develop consensus.
PMID- 22047596
TI - Negative faradaic resistance in extracellular electron transfer by anode
respiring Geobacter sulfurreducens cells.
AB - Geobacter sulfurreducens is a gram-negative delta-proteobacterium that is capable
of transferring respiratory electrons to solid-state extracellular acceptors,
including anodes, via abundant c-type cytochromes expressed in the outer
membrane. As extracellular electron transfer (EET) to solid-state acceptors can
proceed without the addition of exogenous mediators, this microbe has attracted
significant attention with respect to energy conversion between electrical and
chemical energy. Here, we revealed that clear redox peaks were present in the
whole-cell cyclic voltammogram of G. sulfurreducens at around -0.15 V vs Ag|AgCl
when tin-doped In(2)O(3) (ITO) glass was used as an anode. Interestingly, the EET
current decreased in the potential region more positive than the midpoint
potential (E(m)) of the redox peak. Thus, EET of anode-respiring G.
sulfurreducens cells exhibited a negative Faradaic resistance (NFR)
characteristic at the E(m) of the redox peak, in contrast to general
electrochemical systems where the Faradaic current typically increases with
increasing overpotential.
PMID- 22047597
TI - The effect of 670-nm low laser therapy on herpes simplex type 1.
AB - OBJECTIVE: The purpose of this work was to study the effect of low-level laser
therapy (LLLT) on the healing and relapse intervals in patients with recurrent
labial herpes simplex infections. BACKGROUND DATA: Several pharmaceuticals are
available to reduce symptoms and improbe healing of labial herpes, but only LLLT
has been reported to significantly influence the length of the recurrence period.
MATERIAL AND METHODS: In an initial study, 232 patients with herpes simplex type
1 virus symptoms were consecutively selected for either LLLT or conventional
therapy, including acyclovir cream or tablets. One of the dentists was
responsible for the diagnosis, a second dentist for the treatment, and and a
third for the evaluation, to allow for a semi-blinded procedure. Patients in the
laser group received 670-nm laser irradiation, 40 mW, 1.6 J, 2.04 J/cm(2), 51
mW/cm(2) per blister in the prodromal stage and 4.8 J in the crust and
secondarily infected stages, plus 1.2 J at the C2-C3 vertebrae. Patients were
monitored daily during the first week to control healing, and monthly for 1 year
to check on recurrence. In a consecutive study, 322 patients receiving LLLT were
followed during 5 years to observe the period of ocurrences. RESULTS: An obvious
effect of LLLT was found for both initial healing and for the length of the
recurrence periods. CONCLUSIONS: LLLTof herpes simples virus 1 (HSV-1) appears to
be an effective treatment modality without any observed side effects.
PMID- 22047598
TI - Focal increase in cerebral blood flow after treatment with near-infrared light to
the forehead in a patient in a persistent vegetative state.
AB - OBJECTIVE: This study aimed to quantify the cerebral blood flow (CBF) after
bilateral, transcranial near-infrared light-emitting diode (LED) irradiation to
the forehead in a patient in a persistent vegetative state following severe head
injury. BACKGROUND DATA: Positive behavioral improvement has been observed
following transcranial near-infrared light therapy in humans with chronic
traumatic brain injury and acute stroke. METHODS: Single-photon emission computed
tomography with N-isopropyl-[123I]p-iodoamphetamine (IMP-SPECT) was performed
following a series of LED treatments. RESULTS: IMP-SPECT showed unilateral, left
anterior frontal lobe focal increase of 20%, compared to the pre-treatment value
for regional CBF (rCBF) for this area, following 146 LED treatments over 73 days
from an array of 23*850 nm LEDs, 13 mW each, held 5 mm from the skin, 30 min per
session, the power density 11.4 mW/cm(2); the energy density 20.5 J/cm(2) at the
skin. The patient showed some improvement in his neurological condition by moving
his left arm/hand to reach the tracheostomy tube, post-LED therapy. CONCLUSIONS:
Transcranial LED might increase rCBF with some improvement of neurological
condition in severely head-injured patients. Further study is warranted.
PMID- 22047599
TI - Treatment of perianal condyloma acuminate with topical ALA-PDT combined with
curettage: outcome and safety.
AB - OBJECTIVE: The purpose of this study was to evaluate the treatment outcome and
safety of topical photodynamic therapy (PDT) with aminolevulinic acid (5-ALA)
combined with surgical curettage for perianal condyloma acuminata. BACKGROUND
DATA: Condyloma acuminata is the most common sexually transmitted disease, with a
high relapse rate, especially in the perianal area. The outcomes of many
treatment methods for perianal genital warts are not satisfactory. METHODS: In
this study, 40 cases of perianal condyloma acuminata were treated with topical
aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage.
First, the warts were removed with the patient under local anesthesia. The depth
of the ablation and curettage reached the dermal layer. Then, the first session
of PDT was performed after 2 days. Ten percent 5-ALA cream was applied to
lesional skin with occlusive dressing for a 3-h incubation period and the lesions
of warts were irradiated for 10 min by using a 635-nm laser beam of 177 mW/cm(2)
intensity. The ALA-PDT was repeated after 1 and 3 weeks. Follow-up evaluation was
performed at our outpatient clinic at 1 and 3 months after completion of therapy.
Before treatment and at each follow-up visit, the lesions were photographed; the
treatment outcome was evaluated as recurrence rate, and patient satisfaction was
surveyed. RESULTS: After three PDT sessions following surgical curettage, all 40
patients were cured and there was no recurrence at 1 month off treatment. At 3
months off treatment, six cases relapsed, corresponding to a recurrent rate of
15%. The satisfaction rate of patients was 100% at 1 month and 95% at 3 months
after treatment. CONCLUSIONS: Combination of surgical curettage and topical PDT
has been proven to be a safe and effective procedure, and may offer a wide
clinical application for the treatment of perianal condyloma acuminata.
PMID- 22047600
TI - Building the capacity of family day care educators to promote children's social
and emotional wellbeing: an exploratory cluster randomised controlled trial.
AB - BACKGROUND: Childhood mental health problems are highly prevalent, experienced by
one in five children living in socioeconomically disadvantaged families. Although
childcare settings, including family day care are ideal to promote children's
social and emotional wellbeing at a population level in a sustainable way, family
day care educators receive limited training in promoting children's mental
health. This study is an exploratory wait-list control cluster randomised
controlled trial to test the appropriateness, acceptability, cost, and
effectiveness of "Thrive," an intervention program to build the capacity of
family day care educators to promote children's social and emotional wellbeing.
Thrive aims to increase educators' knowledge, confidence and skills in promoting
children's social and emotional wellbeing. METHODS/DESIGN: This study involves
one family day care organisation based in a low socioeconomic area of Melbourne.
All family day care educators (term used for registered carers who provide care
for children for financial reimbursement in the carers own home) are eligible to
participate in the study. The clusters for randomisation will be the fieldworkers
(n = 5) who each supervise 10-15 educators. The intervention group (field workers
and educators) will participate in a variety of intervention activities over 12
months, including workshops; activity exchanges with other educators; and focused
discussion about children's social and emotional wellbeing during field worker
visits. The control group will continue with their normal work practice. The
intervention will be delivered to the intervention group and then to the control
group after a time delay of 15 months post intervention commencement. A baseline
survey will be conducted with all consenting educators and field workers (n =
~70) assessing outcomes at the cluster and individual level. The survey will also
be administered at one month, six months and 12 months post-intervention
commencement. The survey consists of questions measuring perceived levels of
knowledge, confidence and skills in promoting children's social and emotional
wellbeing. As much of this intervention will be delivered by field workers, field
worker-family day care educator relationships are key to its success and thus
supervisor support will also be measured. All educators will also have an in-home
quality of care assessment at baseline, one month, six months and 12 months post
intervention commencement. Process evaluation will occur at one month, six months
and 12 months post-intervention commencement. Information regarding intervention
fidelity and economics will also be assessed in the survey. DISCUSSION: A
capacity building intervention in child mental health promotion for family day
care is an essential contribution to research, policy and practice. This
initiative is the first internationally, and essential in building an evidence
base of interventions in this extremely policy-timely setting. TRIAL REGISTRATION
NUMBER: 343312.
PMID- 22047601
TI - SNOntology: Myriads of novel snoRNAs or just a mirage?
AB - BACKGROUND: Small nucleolar RNAs (snoRNAs) are a large group of non-coding RNAs
(ncRNAs) that mainly guide 2'-O-methylation (C/D RNAs) and pseudouridylation
(H/ACA RNAs) of ribosomal RNAs. The pattern of rRNA modifications and the set of
snoRNAs that guide these modifications are conserved in vertebrates. Nearly all
snoRNA genes in vertebrates are localized in introns of other genes and are
processed from pre-mRNAs. Thus, the same promoter is used for the transcription
of snoRNAs and host genes. RESULTS: The series of studies by Dahai Zhu and
coworkers on snoRNAs and their genes were critically considered. We present
evidence that dozens of species-specific snoRNAs that they described in
vertebrates are experimental artifacts resulting from the improper use of
Northern hybridization. The snoRNA genes with putative intrinsic promoters that
were supposed to be transcribed independently proved to contain numerous
substitutions and are, most likely, pseudogenes. In some cases, they are
localized within introns of overlooked host genes. Finally, an increased number
of snoRNA genes in mammalian genomes described by Zhu and coworkers is also an
artifact resulting from two mistakes. First, numerous mammalian snoRNA
pseudogenes were considered as genes, whereas most of them are localized outside
of host genes and contain substitutions that question their functionality.
Second, Zhu and coworkers failed to identify many snoRNA genes in non-mammalian
species. As an illustration, we present 1352 C/D snoRNA genes that we have
identified and annotated in vertebrates. CONCLUSIONS: Our results demonstrate
that conclusions based only on databases with automatically annotated ncRNAs can
be erroneous. Special investigations aimed to distinguish true RNA genes from
their pseudogenes should be done. Zhu and coworkers, as well as most other groups
studying vertebrate snoRNAs, give new names to newly described homologs of human
snoRNAs, which significantly complicates comparison between different species. It
seems necessary to develop a uniform nomenclature for homologs of human snoRNAs
in other vertebrates, e.g., human gene names prefixed with several-letter code
denoting the vertebrate species.
PMID- 22047602
TI - Development of a cultivation process for the enhancement of human interferon
alpha 2b production in the oleaginous yeast, Yarrowia lipolytica.
AB - BACKGROUND: As an oleaginous yeast, Yarrowia lipolytica is able to assimilate
hydrophobic substrates. This led to the isolation of several promoters of key
enzymes of this catabolic pathway. Less is known about the behavior of Y.
lipolytica in large bioreactors using these substrates. There is therefore a lack
of established know-how concerning high cell density culture protocols of this
yeast. Consequently, the establishment of suitable induction conditions is
required, to maximize recombinant protein production under the control of these
promoters. RESULTS: Human interferon alpha2b (huIFN alpha2b) production in
Yarrowia lipolytica was used as a model for the enhancement of recombinant
protein production under the control of the oleic acid (OA)-inducible promoter
POX2. Cell viability and heterologous protein production were enhanced by
exponential glucose feeding, to generate biomass before OA induction. The optimal
biomass level before induction was determined (73 g L(-1)), and glucose was added
with oleic acid during the induction phase. Several oleic acid feeding strategies
were assessed. Continuous feeding with OA at a ratio of 0.02 g OA per g dry cell
weight increased huIFNalpha2b production by a factor of 1.88 (425 mg L(-1)) and
decreased the induction time (by a factor of 2.6, 21 h). huIFN alpha2b
degradation by an aspartic protease secreted by Y. lipolytica was prevented by
adding pepstatin (10 MUM), leading to produce a 19-fold more active huIFN alpha2b
(26.2 * 10(7) IU mg(-1)). CONCLUSION: Y. lipolytica, a generally regarded as safe
(GRAS) microorganism is one of the most promising non conventional yeasts for the
production of biologically active therapeutic proteins under the control of
hydrophobic substrate-inducible promoter.
PMID- 22047603
TI - Aligning nanodiscs at the air-water interface, a neutron reflectivity study.
AB - Nanodiscs are self-assembled nanostructures composed of a belt protein and a
small patch of lipid bilayer, which can solubilize membrane proteins in a lipid
bilayer environment. We present a method for the alignment of a well-defined two
dimensional layer of nanodiscs at the air-water interface by careful design of an
insoluble surfactant monolayer at the surface. We used neutron reflectivity to
demonstrate the feasibility of this approach and to elucidate the structure of
the nanodisc layer. The proof of concept is hereby presented with the use of
nanodiscs composed of a mixture of two different lipid (DMPC and DMPG) types to
obtain a net overall negative charge of the nanodiscs. We find that the nanodisc
layer has a thickness or 40.9 +/- 2.6 A with a surface coverage of 66 +/- 4%.
This layer is located about 15 A below a cationic surfactant layer at the air
water interface. The high level of organization within the nanodiscs layer is
reflected by a low interfacial roughness (~4.5 A) found. The use of the nanodisc
as a biomimetic model of the cell membrane allows for studies of single membrane
proteins isolated in a confined lipid environment. The 2D alignment of nanodiscs
could therefore enable studies of high-density layers containing membrane
proteins that, in contrast to membrane proteins reconstituted in a continuous
lipid bilayer, remain isolated from influences of neighboring membrane proteins
within the layer.
PMID- 22047604
TI - Positioning of bound electron wave packets in molecules revealed by high-harmonic
spectroscopy.
AB - By solution of the time-dependent two-electron Schrodinger equation, we
demonstrate that strong-field ionization in combination with electron correlation
can localize bound electron wave packets in molecules. The wave packet creation
is revealed by the emission spectrum in high-order harmonic generation, which is
sensitive to the ionization and recombination phase difference between different
ionization channels. For hydrogen molecules at stretched internuclear distance,
we find that the ionization phase difference between the gerade and ungerade
channels is in the range from pi and 1.5pi, indicating that the bound wave packet
either is initially on the same side as the outgoing electron or is delocalized.
PMID- 22047605
TI - Spectral characterization of guanine C4-OH adduct: a radiation and quantum
chemical study.
AB - The reaction of hydroxyl radical ((*)OH) with guanine was investigated under
restricted pH condition (pH 4.6) using pulse radiolysis technique. The time
resolved optical transient absorption spectra showed two peaks centered at 300
and 330 nm at 4 MUs after the pulse which exhibited different reactivity toward
molecular oxygen (O(2)). The peak at 300 nm was found to be relatively more
stable than the peak at 330 nm. The peak corresponding to 330 nm decayed within
20 MUs having a first order rate constant 4-7 * 10(4) s(-1) and was pH dependent.
On longer time scale, the species decayed by a bimolecular process. The presence
of O(2) did not affect its decay rate constant. The (*)OH reacts with guanine at
pH 4.6 with a diffusion-controlled second order rate constant of >=1 * 10(10)
mol(-1) dm(3) s(-1). The reaction of Br(2)(*-), O(2)(*-), and 2-hydroxy-2-propyl
radical with guanine was also investigated to differentiate among the one
electron oxidized, one-electron reduced species of guanine and the guanine-OH
adducts formed in the reaction of (*)OH at pH 4.6. On the basis of the spectral
characteristics and reactivity toward O(2), two guanine-OH adduct species were
identified (i) the C4-OH adduct species absorbing at 330 nm which has not been
reported so far and (ii) the C8-OH adduct species absorbing at 300 nm in
agreement with the known literature absorption features. Quantum chemical
calculations using BHandHLYP with 6-31+G(d,p) basis set and excited state
calculations using TDDFT for all possible transients complement the assignment of
the observed spectral peak at 330 nm to the C4-OH adduct of guanine. Furthermore,
steady state radiolysis revealed the formation of 8-hydroxy-guanine whose
precursor is known to be the C8-OH adduct species.
PMID- 22047606
TI - Targeting the binding function 3 (BF3) site of the human androgen receptor
through virtual screening.
AB - The androgen receptor (AR) is the best studied drug target for the treatment of
prostate cancer. While there are a number of drugs that target the AR, they all
work through the same mechanism of action and are prone to the development of
drug resistance. There is a large unmet need for novel AR inhibitors which work
through alternative mechanism(s). Recent studies have identified a novel site on
the AR called binding function 3 (BF3) that is involved into AR transcriptional
activity. In order to identify inhibitors that target the BF3 site, we have
conducted a large-scale in silico screen followed by experimental evaluation. A
number of compounds were identified that effectively inhibited the AR
transcriptional activity with no obvious cytotoxicity. The mechanism of action of
these compounds was validated by biochemical assays and X-ray crystallography.
These findings lay a foundation for the development of alternative or
supplementary therapies capable of combating prostate cancer even in its
antiandrogen resistant forms.
PMID- 22047607
TI - A strategy for emergency treatment of Schistosoma japonicum-infested water.
AB - BACKGROUND: Schistosomiasis japonica, caused by contact with Schistosoma
japonicum cercaria-infested water when washing, bathing or production, remains a
major public-health concern in China. The purpose of the present study was to
investigate the effect of a suspension concentrate of niclosamide (SCN) on
killing cercaria of S. japonicum that float on the water surface, and its
toxicity to fish, so as to establish an emergency-treatment intervention for
rapidly killing cercaria and eliminating water infectivity. RESULTS: At 30 min
after spraying 100 mg/L SCN, with niclosamide dosages of 0.01, 0.02, 0.03, 0.04
g/m2, the water infectivity reduced significantly and no infectivity was found at
60 min after spraying SCN. The surface of static water was sprayed with 100 mg/L
SCN, the peak concentration was found at 0 min, and the solution diffused to site
with a water depth of 10 cm after 10 min. 30 min later, SCN diffused to the whole
water body, and distributed evenly. After spraying 100 mg/L SCN onto the surface
of the water with a volume of(3.14 * 202 * 50)cm3, with niclosamide dosages of
0.02 g/m2, 96 h later, no death of zebra fish was observed. CONCLUSIONS: By
spraying 100 mg/L SCN, with a niclosamide dosage of 0.02 g/m2 onto the surface of
S. japonicum-infested water, infectivity of the water can be eliminated after 30
60 min, and there is no evident toxicity to fish. This cercaria-killing method,
as an emergency-treatment intervention for infested water, can be applied in
those forecasting and early warning systems for schistosomiasis.
PMID- 22047608
TI - Tumor necrosis factor (TNF)-alpha upregulates progesterone receptor-A by
activating the NF-kappaB signaling pathway in human decidua after labor onset.
AB - To date, the relationship between inflammatory cytokines and progesterone
receptors (PRs) has been little studied, although both mediate the mechanism of
parturition in human deciduas. Thus, the aim of study was to investigate the role
of an inflammatory cytokine, tumor necrosis factor (TNF)-alpha, in regulating
progesterone withdrawal in decidua at human parturition. TNF-alpha levels and PR
isoforms were compared in intrauterine deciduas from women who were in labor (IL,
n = 10) or who were not in labor (NIL, n = 10). Nuclear factor-kappaB (NF-kappaB)
signaling and PR status were analyzed in NIL deciduas after TNF-alpha
stimulation. Immunohistochemistry, western blotting, ELISA and reverse
transcription-polymerase chain reaction (RT-PCR) were used to localize and
quantitate protein and mRNA expression. TNF-alpha immunostaining, protein levels,
PR-A/PR-B ratio and COX-2 level were significantly higher in IL deciduas (all P <
0.05). NF-kappaB was activated by TNF-alpha after 24 h stimulation in a dose
dependent manner, and was significantly inactivated by the NF-kappaB inhibitor
panepoxydone, which was associated with decreased PR-A and COX-2 expression (P <
0.05) in not in labor deciduas. In conclusion, TNF-alpha may have an important
role in regulating progesterone withdrawal in human decidua following labor
onset.
PMID- 22047609
TI - The impact of comorbid cannabis use disorders on the clinical presentation of
social anxiety disorder.
AB - Previous research has examined the relationship between social anxiety disorder
(SAD) and substance use disorders. Cannabis use disorders (CUDs) are becoming
increasingly problematic within the population of individuals with SAD, yet the
nature of this comorbidity remains largely unexamined. The aim of the current
study from the Rhode Island Methods to Improve Diagnostic Assessment and Services
(MIDAS) project was to examine differences between outpatients with SAD with
versus without comorbid CUDs. The current study included 873 outpatients with a
current diagnosis of SAD. Patients with SAD and comorbid CUDs (n = 173) were then
compared to those with SAD without CUDs (n = 700) on demographic and clinical
characteristics. Compared to patients without the comorbidity, patients with
comorbid SAD and CUDs were more likely to have a lifetime diagnosis of PTSD and
specific phobia and lifetime substance use disorders (including alcohol). SAD
patients with comorbid CUDs were also more likely to report better physical
health, and fewer limitations related to their physical health. These analyses
remained significant after controlling for gender, the presence of other
substance use disorders, mood disorders, and other anxiety disorders. Findings of
this study suggest that there may be a unique relationship between SAD and CUDs
that can potentially impact the clinical presentation of individuals with SAD.
Future research is needed to examine the impact of this comorbidity in other
patient populations.
PMID- 22047610
TI - Consumers' salient beliefs regarding dairy products in the functional food era: a
qualitative study using concepts from the theory of planned behaviour.
AB - BACKGROUND: Inadequate consumption of dairy products without appropriate dietary
substitution may have deleterious health consequences. Social research reveals
the factors that may impede compliance with dietary recommendations. This is
particularly important given the recent introduction of functional dairy
products. One of the challenges for public health professionals is to demonstrate
the efficacy of nutrition education in improving attitudes toward nutrient rich
foods. The aim of this study was to explore the salient beliefs of adult weight
loss trial participants regarding both traditional and functional dairy products
and to compare these with a control group not exposed to nutrition education.
METHODS: Six focus groups were conducted, three with weight loss trial completers
(n = 15) that had received nutrition education and three with individuals from
the same region (n = 14) to act as controls. Transcribed focus groups were coded
using the Theory of Planned Behaviour theoretical framework. RESULTS: Non-trial
participants perceived dairy foods as weight inducing and were sceptical of
functional dairy products. A lack of time/ability to decipher dairy food labels
was also discussed by these individuals. In contrast trial participants discussed
several health benefits related to dairy foods, practised label reading and were
confident in their ability to incorporate dairy foods into their diet. Normative
beliefs expressed were similar for both groups indicating that these were more
static and less amenable to change through nutrition education than control and
behavioural beliefs. CONCLUSIONS: Nutrition education provided as a result of
weight loss trial participation influenced behavioural and control beliefs
relating to dairy products. This study provides a proof of concept indication
that nutrition education may improve attitudes towards dairy products and may
thus be an important target for public health campaigns seeking to increase
intake of this food group.
PMID- 22047611
TI - Control of the photocatalytic activity of bimetallic complexes of
pyropheophorbide-a by nucleic acids.
AB - Photocatalytic activity of a photosensitizer (PS) in an oligodeoxyribonucleotide
duplex 5'-PS~ODN1/ODN2~Q-3' is inhibited because of close proximity of a quencher
Q. The ODN2 in this duplex is selected to be longer than the ODN1. Therefore, in
the presence of a nucleic acid (analyte), which is fully complementary to the
ODN2 strand, the duplex is decomposed with formation of an analyte/ODN2~Q duplex
and a catalytically active, single stranded PS~ODN1. In this way the catalytic
activity of the PS can be controlled by the specific nucleic acids. We applied
this reaction earlier for the amplified detection of ribonucleic acids in live
cells (Arian, D.; Clo, E.; Gothelf, K.; Mokhir, A. Chem.-Eur. J.2010, 16(1),
288). As a photosensitizer (PS) we used In(3+)(pyropheophorbide-a)chloride and as
a quencher (Q)--Black-Hole-Quencher-3 (BHQ-3). The In(3+) complex is a highly
active photocatalyst in aqueous solution. However, it can coordinate additional
ligands containing thiols (e.g., proteins, peptides, and aminoacids), that
modulate properties of the complex itself and of the corresponding bio-
molecules. These possible interactions can lead to undesired side effects of
nucleic acid controlled photocatalysts (PS~ODN1/ODN2~Q) in live cells. In this
work we explored the possibility to substitute the In(3+) complex for those ones
of divalent metal ions, Zn(2+) and Pd(2+), which exhibit lower or no tendency to
coordinate the fifth ligand. We found that one of the compounds tested
(Pd(pyropheophorbide-a) is as potent and as stable photosensitizer as its In(3+)
analogue, but does not coordinate additional ligands that makes it more suitable
for cellular applications. When the Pd complex was introduced in the duplex
PS~ODN1/ODN2~Q as a PS, its photocatalytic activity could be controlled by
nucleic acids as efficiently as that of the corresponding In(3+) complex.
PMID- 22047612
TI - Northeastern Section of the American Urological Association 63(rd) Annual
Meeting, New Orleans, Louisiana October 26 - 30, 2011 Scientific Program.
PMID- 22047613
TI - Products of SO2 adsorption on fuel cell electrocatalysts by combination of sulfur
K-edge XANES and electrochemistry.
AB - Electrochemical adsorption of SO(2) on platinum is complicated by the change in
sulfur oxidation state with potential. Here, we attempt to identify SO(2)
adsorption products on catalyst coated membranes (CCMs) at different electrode
potentials using a combination of in situ sulfur K-edge XANES (X-ray absorption
near-edge structure) spectroscopy and electrochemical techniques. CCMs employed
platinum nanoparticles supported on Vulcan carbon (Pt/VC). SO(2) was adsorbed
from a SO(2)/N(2) gas mixture while holding the Pt/VC-electrode potential at 0.1,
0.5, 0.7, and 0.9 V vs a reversible hydrogen electrode (RHE). Sulfur adatoms
(S(0)) are identified as the SO(2) adsorption products at 0.1 V, while mixtures
of S(0), SO(2), and sulfate/bisulfate ((bi)sulfate) ions are suggested as SO(2)
adsorption products at 0.5 and 0.7 V. At 0.9 V, SO(2) is completely oxidized to
(bi)sulfate ions. The identity of adsorbed SO(2) species on Pt/VC catalysts at
different electrode potentials is confirmed by modeling of XANES spectra using
FEFF8 and a linear combination of experimental spectra from sulfur standards.
Results on SO(2) speciation gained from XANES are used to compare platinum-sulfur
electronic interactions for Pt(3)Co/VC versus Pt/VC catalysts in order to
understand the difference between the two catalysts in terms of SO(2)
contamination.
PMID- 22047614
TI - A case of hybrid closure of a muscular ventricular septal defect: anatomical
complexity and surgical management.
AB - Complex muscular ventricular septal defect poses difficult surgical management
and is associated with high morbidity and mortality despite advancements in
surgical therapy. Device closure of muscular ventricular septal defect has been
encouraging and has been used in hybrid approach at a few centres. However,
device closure has some limitations in patients with complex muscular ventricular
septal defect. We report a case of perventricular device closure of a complex
muscular ventricular septal defect in a beating heart with entrapped right
ventricular disc and its surgical management.
PMID- 22047615
TI - Modifications of the metabolic pathways of lipid and triacylglycerol production
in microalgae.
AB - Microalgae have presented themselves as a strong candidate to replace diminishing
oil reserves as a source of lipids for biofuels. Here we describe successful
modifications of terrestrial plant lipid content which increase overall lipid
production or shift the balance of lipid production towards lipid varieties more
useful for biofuel production. Our discussion ranges from the biosynthetic
pathways and rate limiting steps of triacylglycerol formation to enzymes required
for the formation of triacylglycerol containing exotic lipids. Secondarily, we
discuss techniques for genetic engineering and modification of various microalgae
which can be combined with insights gained from research in higher plants to aid
in the creation of production strains of microalgae.
PMID- 22047617
TI - Organochlorine contaminants in the hair of Iranian pregnant women.
AB - In the present study, the hair of pregnant women was sampled between November
2007 and January 2008 in Ahvaz and Noushahr cities and the countryside of
Noushahr, Iran. They were analyzed for organochlorine pesticides (OCPs), such as
dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene
(HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) isomers and seven
polychlorinated (PCBs) congeners (IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180).
Significant differences between the concentrations of investigated pollutants
were found between the locations (p<0.05). For HCHs, the gamma-HCH isomer was
measured at higher mean concentrations (6 ng g(-1) hair) compared to the beta-HCH
isomer (0.03 ng g(-1)), which generally is the most prevalent HCH in biological
matrices. Very high mean concentrations of p,p'-DDT in countryside of Noushahr
(24 ng g(-1)) combined with lower values (0.6) of ratio p,p'-DDE/p,p'-DDT in the
hair samples suggest recent exposure to "fresh" DDT in this region. Significant
differences in OCPs and PCBs were found between primiparous and multiparous
mothers (p<0.05). There was no correlation between levels of OCPs and PCBs in the
hair of Iranian pregnant women and their age. There was a significant difference
(p<0.05) in the organochlorine levels, including HCHs, between mothers who have
eaten fish once a week and those who consumed fish more than once per week in
Noushahr.
PMID- 22047616
TI - Prediction of RNA Polymerase II recruitment, elongation and stalling from histone
modification data.
AB - BACKGROUND: Initiation and elongation of RNA polymerase II (RNAPII) transcription
is regulated by both DNA sequence and chromatin signals. Recent breakthroughs
make it possible to measure the chromatin state and activity of core promoters
genome-wide, but dedicated computational strategies are needed to progress from
descriptive annotation of data to quantitative, predictive models. RESULTS: Here,
we describe a computational framework which with high accuracy can predict the
locations of core promoters, the amount of recruited RNAPII at the promoter, the
amount of elongating RNAPII in the gene body, the mRNA production originating
from the promoter and finally also the stalling characteristics of RNAPII by
considering both quantitative and spatial features of histone modifications
around the transcription start site (TSS).As the model framework can also
pinpoint the signals that are the most influential for prediction, it can be used
to infer underlying regulatory biology. For example, we show that the H3K4 di-
and tri- methylation signals are strongly predictive for promoter location while
the acetylation marks H3K9 and H3K27 are highly important in estimating the
promoter usage. All of these four marks are found to be necessary for recruitment
of RNAPII but not sufficient for the elongation. We also show that the spatial
distributions of histone marks are almost as predictive as the signal strength
and that a set of histone marks immediately downstream of the TSS is highly
predictive of RNAPII stalling. CONCLUSIONS: In this study we introduce a general
framework to accurately predict the level of RNAPII recruitment, elongation,
stalling and mRNA expression from chromatin signals. The versatility of the
method also makes it ideally suited to investigate other genomic data.
PMID- 22047618
TI - Biotic transformation of anticoccidials in soil using a lab-scale bio-reactor as
a precursor-tool.
AB - Two anticoccidial agents, salinomycin and robenidine, heavily used in the
worldwide veterinary meat production, were investigated for their potential
biotic degradation by cultured soil bacteria. The degradation-study was performed
in lab-scale bio-reactors under aerobic and anaerobic conditions incubated for
200 h with a mixed culture of soil bacteria. Samples were analyzed by LC-MS/MS
and potential transformation products were tentatively identified. Salinomycin
was degraded under aerobic conditions and traces could be found after 200 h,
however, seems more persistent under anaerobic conditions. Four transformation
products of salinomycin were discovered. Robenidine was degraded under aerobic
and anaerobic conditions, however, traces of robenidine were observed after 200
h. Five biotic transformation products of robenidine were discovered.
PMID- 22047619
TI - High frequency of diastolic dysfunction in a population-based cohort of elderly
women--but poor association with the symptom dyspnea.
AB - BACKGROUND: The European Society of Cardiology recently proposed a new algorithm
"How to diagnose heart failure with normal ejection fraction". Central element of
the diagnostic strategy is the demonstration of diastolic dysfunction, either by
tissue Doppler-derived indices in first line, or in second line by a combination
of elevated blood levels of natriuretic peptide with abnormal tissue Doppler
findings. We thought to use this diagnostic flowchart in a population-based
cohort of elderly women, in whom the prevalence of diastolic dysfunction and
heart failure is believed to be high. The purpose was to evaluate the association
of dyspnea with the presence of diastolic dysfunction. METHODS: The study cohort
recruited from a cross-sectional follow-up examination of the SALIA cohort (study
on the influence of air pollution on lung function, inflammation, and aging).
Participants with cardiac or pulmonary disease were excluded, 291 participants
formed the final study group (all women, age range 69 to 79 years, all in sinus
rhythm, LV ejection fraction > 50%, LV enddiastolic volume index < 97 mL/m2).
Quality of life was assessed by the Minnesota living with heart failure
questionnaire, and actual symptoms by a structural questionnaire; the examination
consisted of a physical examination, measurement of B-type natriuretic peptide,
ECG and tissue Doppler echocardiography. Diastolic dysfunction was assumed when
the E/E' ratio exceeded 15 as derived from tissue Doppler. In case, tissue
Doppler yielded an E/E' ratio ranging from 8 to 15, additional non-invasive
parameters had to be fulfilled: left atrial volume index > 40 ml/m2 body surface,
or left ventricular mass index > 122 g/m2 body surface, or transmitral E/A ratio
< 0.5 plus deceleration time > 280 ms, or blood level of brain natriuretic
peptide (BNP) > 200 pg/mL. RESULTS: The examinations were concordant with the
presence of diastolic dysfunction in 122/291 participants (41.9%). The diagnosis
based in 94% of cases on two criteria: in 50 cases on the criterion "E/E' ratio >
15", and in 65 cases on the criterion "15 > E/E'>8 and LV mass index > 122 g/m2".
The participants with diastolic dysfunction had on average a higher body mass
index, more frequent a history of arterial hypertension and of hospitalization
for congestive heart failure, poorer quality of life, and higher BNP blood levels
as compared to those participants without signs of diastolic dysfunction. The
number of participants complaining exertional dyspnea, however, was similar
distributed among the subgroups with and without signs of diastolic dysfunction
(40.2 vs 40.8%; p = n.s). In a logistic regression model, the symptom dyspnea was
best predicted by systolic pulmonary artery pressure, followed by left atrial
volume index, BNP, and body mass index. CONCLUSION: The demonstration of
diastolic dysfunction showed only a poor association with the symptom dyspnea in
a cohort of elderly women with otherwise normal systolic function. Additional
structural or hemodynamic changes are necessary to "explain" the symptom dyspnea.
It is unclear whether these additional factors are secondary to a more advanced
stage of diastolic dysfunction, or are related to cardiovascular co-morbidities,
or both.
PMID- 22047620
TI - Ferret islet amyloid polypeptide (IAPP): characterization of in vitro and in vivo
amyloidogenicity.
AB - Diabetes in the domestic ferret (Mustela putorius furo) has previously been
described and the purpose of this study was to evaluate if the ferret could serve
as a model for the study of beta-cell degeneration associated with formation of
islet amyloid. The nucleotide and amino acid sequence of ferret islet amyloid
polypeptide (IAPP) 1-37 was identified and the synthesized peptide was studied
with regards to in vitro amyloidogenicity and potential cellular toxicity in a
comparative approach to human, cat and the nonamyloidogenic rat IAPP. Ferret IAPP
forms amyloid-like fibrils, but with a longer lag phase than human and cat IAPP
and the aggregation process was shown to reduce cell viability of cultured beta
cells, but with less potency than these two amyloidogenic counterparts.
Immunohistochemistry of ferret pancreas confirmed IAPP expression in the islets
of Langerhans, but no islet amyloid was found in a very limited sample size of
one diabetic and five healthy ferrets. Islet amyloid has never been described in
ferrets, and it is not possible to determine if it is due to lack of
studies/material or to the fact that the ferret's life span is too short to
present with such pathology.
PMID- 22047621
TI - [The Act of Promotion of Personal Autonomy and Long-Term Care. Reflections and
recommendations for better development].
AB - The present article provides a critical analysis of the state of affairs of the
care of dependent individuals and proposals for reform of social protection
systems for dependency - especially the Act of Promotion of Personal Autonomy and
Long-Term Care. The existing form of public coverage is linked to the theory of
public finance. Against this background, a series of recommendations are made to
achieve the goals of this important component of the welfare state.
PMID- 22047622
TI - Incidence of colorectal cancer and influence of dietary habits in fifteen
European countries from 1971 to 2002.
AB - OBJECTIVE: This study aimed to analyze the incidence of colorectal cancer in 15
European countries in recent decades and the relationship between the incidence
found and changes in dietary habits. METHODS: Pearson's or Spearman's correlation
coefficients were calculated by comparing incidence rates obtained from the
International Agency for Research on Cancer for 1971-2002 with data on per capita
consumption obtained from the Food and Agriculture Organization of the United
Nations using 10-year delay intervals. RESULTS: Incidence rates increased in all
countries except France in men and except Austria, Denmark, England and France in
women. Of the dietary variables considered, there were marked increasing trends
(linear regression coefficient, R >=0.5) in red meat consumption in Germany (R =
0.9), Austria (R = 0.7), Finland (R = 0.8), Italy (R = 0.9), Poland (R = 0.5),
Spain (R = 2.1), Sweden (R = 0.6), and the Netherlands (R = 0.7). CONCLUSIONS:
Changes in dietary habits may be consistent with the observed trends in the
incidence of colorectal cancer in the distinct European countries.
PMID- 22047623
TI - [Research in primary care as an area of knowledge. SESPAS Report 2012].
AB - Primary care offers huge potential for research. This setting is an area of
knowledge that must expand to improve the quality of its services and patients'
health. Population-based clinical studies with a focus on health promotion and
primary, secondary and tertiary disease prevention offer unique research
opportunities. Developing research in the biopsychosocial model of clinical
practice and new models of integrated healthcare and community care is therefore
a priority. The framework and activities carried out by the Research Network in
Preventive Activities and Health Promotion have been instrumental in the
development of research in primary care in Spain. Despite the efforts invested by
various institutions, foundations, teaching and research departments in primary
care research, the projected outputs in terms of volume, quality and impact have
not been achieved. The involvement of primary care professionals in research
platforms is insufficient, with scarce contribution toward investment in specific
primary care research projects. To change the current status of research in
primary care, a number of measures are required, namely, the consolidation of
research organisms specific to primary care with adequate allocation of funding
and staff, and the allocation of specific time for research to primary care
professionals to enable them to produce significant projects and consolidate
established research lines in their areas of expertise, with applications mainly
in quality improvement and innovation of primary care services.
PMID- 22047624
TI - [Attitudes toward online HIV/sexually-transmitted infection prevention programs
and Internet user profiles among men who have sex with men].
AB - OBJECTIVES: To describe the attitudes of men who have sex with men (MSM) toward
online HIV/sexually-transmitted infection (STI) prevention programs and to
identify and characterize user profiles with regard to their attitudes toward
online prevention programs. METHOD: A survey in gay venues or via the internet
was completed by 2,044 participants from Madrid, Barcelona, Bilbao and San
Sebastian (Spain). The survey explored socio-demographic variables, sexual
behavior and other risk behaviors associated with HIV infection, as well as
attitudes toward online prevention programs. The statistical analysis included
factor analysis and non-hierarchical cluster analysis. RESULTS: Most MSM had
positive attitudes towards online HIV/STI prevention programs. Factor analysis
revealed two factors: online prevention aimed at interaction and online
prevention aimed at information. Based on these factors, three user profiles were
identified: users oriented toward informative and interactive online prevention
(53.5%), users oriented toward interactive online prevention (25.9%) and users
were not oriented toward online prevention (20.7%). On characterizing these
profiles, we observed a significant presence of men who were not interested in
online prevention among those with a lower educational level, bisexual men and
HIV-positive men. Conversely, those most receptive to online prevention were men
self-identified as gay, those with a bachelors degree, those who had been tested
for HIV and those who were HIV-negative. CONCLUSION: The internet can facilitate
sexual health promotion among MSM. Characterization of user profiles offers the
possibility of segmenting prevention programs and of combining online and offline
strategies.
PMID- 22047625
TI - [Motivations for tobacco consumption among adolescents in an urban high school].
AB - OBJECTIVE: To determine the motivations (attitudes, beliefs and experiences) for
tobacco consumption among adolescents. METHODS: This study was based on
qualitative methodology using six 50-minute discussion groups with 6-8
adolescents per group during the 2008/09 school year. Purposive sampling was
performed of 12-18 year-old adolescents attending a middle-class urban school
(Jaen, Spain). The sample was stratified by educational level as the homogeneity
criterion and gender and tobacco consumption as the heterogeneity criterion.
Content analysis consisted of coding, triangulation of categories and obtaining
and verifying the results. RESULTS: There were 44 adolescents (54% male). The
participants reported that smoking relaxed and improved self-image, providing
security (boys) and improving relations with the opposite sex, as well as weight
control (girls). The family encouraged smoking by providing a model to imitate,
although many adolescents hid their smoking from their families. Friends
constituted a pressure group to start or continue smoking. Starting secondary
school marked the beginning of experimental use. Society tended to accept
consumption and buying tobacco was easy for minors. University students were a
role model and were free to smoke. The adolescents looked to their parents and
educators/health workers to provide a model of abstinence and reported that they
were well informed but only remembered powerful messages. Participants
unanimously indicated that tobacco causes addiction, but in proportion to the
duration of consumption, and were concerned only with the immediate symptoms
caused by smoking. Teenage smokers associated multiple drug use with leisure
time. CONCLUSIONS: This study provides useful data on motivation that could be
used to improve smoking prevention interventions among adolescents. The most
important factors seem to be peer influence, parental attitudes, easy access to
tobacco and symptoms of dependence.
PMID- 22047626
TI - Oral ezatiostat HCl (Telintra(r), TLK199) and idiopathic chronic neutropenia
(ICN): a case report of complete response of a patient with G-CSF resistant ICN
following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1)
inhibitor.
AB - Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of
hematologic diseases characterized by low circulating neutrophil levels often
associated with recurrent fevers, chronic mucosal inflammation, and severe
systemic infections. The severity and risk of complications, including serious
infections, are inversely proportional to the absolute neutrophil count (ANC),
with the greatest problems occurring in patients with an ANC of less than 0.5 *
109/L. This case report describes a 64-year-old female with longstanding
rheumatoid arthritis who subsequently developed ICN with frequent episodes of
sepsis requiring hospitalization and prolonged courses of antibiotics over a 4
year period. She was treated with granulocyte colony stimulating factors (G-CSF)
but had a delayed, highly variable, and volatile response. She was enrolled in a
clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat,
a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the
growth and maturation of hematopoietic progenitor stem cells. She responded by
the end of the first month of treatment with stabilization of her ANC (despite
tapering and then stopping G-CSF), clearing of fever, and healing of areas of
infection. This ANC response to ezatiostat treatment has now been sustained for
over 8 months and continues. These results suggest potential roles for ezatiostat
in the treatment of patients with ICN who are not responsive to G-CSF, as an oral
therapy alternative, or as an adjunct to G-CSF, and further studies are
warranted.
PMID- 22047627
TI - Understanding physicians' acceptance of the Medline system for practicing
evidence-based medicine: a decomposed TPB model.
AB - PURPOSE: Evidence-based medicine (EBM) supports physicians in their improvement
of clinical quality and enhances hospitals' improvement of patient safety. Many
health care institutions implement information systems to support physicians
practicing EBM. However, studies exploring the antecedent factors of physicians'
usage intention of information systems facilitating EBM practice are rare. Hence
this study proposed a research model based on the decomposed theory of the
planned behavior model (decomposed TPB) to investigate the factors influencing
physicians' acceptance of the Medline system. METHODS: A field survey was
conducted in Taiwan to collect data from physicians with experience in using the
Medline system. A valid sample of 224 physicians was collected for data analysis.
Structural equation modeling using the partial least squares (PLS) method with
bootstrap estimate was used to test the research model. RESULTS: The findings of
this study show that a physician's usage intention is significantly influenced by
three factors, i.e. attitude, the subjective norm, and perceived behavior
control. Furthermore, these three factors can be predicted by perceived
usefulness and perceived ease of use, interpersonal influence, personal
innovativeness in IT and self-efficacy, respectively. CONCLUSIONS: The results of
this study indicate that our research model provides an effective prediction of
the intention of physicians to use the Medline system and provides valuable
implications for academics and practitioners.
PMID- 22047628
TI - Induced oscillatory responses during the Sternberg's visual memory task in
patients with Alzheimer's disease and mild cognitive impairment.
AB - In this study we used magnetoencephalography during a modified version of the
Sternberg's memory recognition task performed by patients with early Alzheimer's
disease (AD), mild cognitive impairment (MCI), and by age-matched healthy
controls to identify differences in induced oscillatory responses. For analyses,
we focused on the retention period of the working memory task. Multiple-source
beamformer and Brain Voyager were used for localization of source-power changes
across the cortex and for statistic group analyses, respectively. We found
significant differences in oscillatory response during the task, specifically in
beta and gamma frequency bands: patients with AD showed reduced beta event
related desynchronization (ERD) in the right central area compared to controls,
and reduced gamma ERD in the left prefrontal and medial parietal cortex compared
to patients with MCI. Our findings suggest that reduced oscillatory responses
over certain brain regions in high frequency bands (i.e., beta, gamma), and
especially in the beta band that was significantly different between AD patients
and healthy subjects, may represent brain electromagnetic changes underlying
visual-object working memory dysfunction in early AD, and a neurophysiological
indicator of cognitive decline.
PMID- 22047629
TI - Polypeptide folding-mediated tuning of the optical and structural properties of
gold nanoparticle assemblies.
AB - Responsive hybrid nanomaterials with well-defined properties are of significant
interest for the development of biosensors with additional applications in tissue
engineering and drug delivery. Here, we present a detailed characterization using
UV-vis spectroscopy and small angle X-ray scattering of a hybrid material
comprised of polypeptide-decorated gold nanoparticles with highly controllable
assembly properties. The assembly is triggered by a folding-dependent bridging of
the particles mediated by the heteroassociation of immobilized helix-loop-helix
polypeptides and a complementary nonlinear polypeptide present in solution. The
polypeptides are de novo designed to associate and fold into a heterotrimeric
complex comprised of two disulfide-linked four-helix bundles. The particles form
structured assemblies with a highly defined interparticle gap (4.8+/-0.4 nm) that
correlates to the size of the folded polypeptides. Transitions in particle
aggregation dynamics, mass-fractal dimensions and ordering, as a function of
particle size and the concentration of the bridging polypeptide, are observed;
these have significant effects on the optical properties of the assemblies. The
assembly and ordering of the particles are highly complex processes that are
affected by a large number of variables including the number of polypeptides
bridging the particles and the particle mobility within the aggregates. A
fundamental understanding of these processes is of paramount interest for the
development of novel hybrid nanomaterials with tunable structural and optical
properties and for the optimization of nanoparticle-based colorimetric
biodetection strategies.
PMID- 22047630
TI - Expression of antimicrobial peptides in diabetic foot ulcer.
AB - BACKGROUND: Foot ulcers are one of the main diabetes complications due to its
high frequency and difficulty of complete healing. There are several factors that
participate in diabetic ulcers development and limited information exists about
the role of antimicrobial peptides (AMP) in its pathogenesis. OBJECTIVE: The aim
of this study was to analyze the expression pattern of the main AMPs: Human
Neutrophil Peptide (HNP)-1, Human beta-defensin (HBD)-1, HBD-2, HBD-3, HBD-4 and
cathelicidin LL-37 in biopsies from diabetic foot ulcers (DFU). METHODS: 20
biopsies from DFU grade 3 according to Wagner's classification and 20 biopsies
from healthy donors were obtained. Real time PCR, immunohistochemistry and
primary cell cultures were performed. RESULTS: beta-Defensins were overexpressed
in DFU, whereas LL-37 has low or none expression in comparison with healthy skin.
When primary cell culture from these biopsies were performed and infected with
Staphylococcus aureus, epidermal cell from diabetic ulcers showed lower LL-37
expression compared with cell cultures from healthy donors skin. CONCLUSION:
These results suggest that though most AMPs are expressed in DFU, this production
is not appropriate to promote wound healing and contain secondary infections.
PMID- 22047631
TI - Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing
for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's
Biomarkers Standardization Initiative.
AB - BACKGROUND: Numerous studies show that the cerebrospinal fluid biomarkers total
tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181P)), and amyloid-beta
(1-42) (Abeta(1-42)) have high diagnostic accuracy for Alzheimer's disease.
Variability in concentrations for Abeta(1-42), T-tau, and P-tau(181P) drives the
need for standardization. METHODS: Key issues were identified and discussed
before the first meeting of the members of the Alzheimer's Biomarkers
Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on
preanalytical issues. RESULTS: Consensus was reached on preanalytical issues such
as the effects of fasting, different tube types, centrifugation, time and
temperature before storage, storage temperature, repeated freeze/thaw cycles, and
length of storage on concentrations of Abeta(1-42), T-tau, and P-tau(181P) in
cerebrospinal fluid. CONCLUSIONS: The consensus reached on preanalytical issues
and the recommendations put forward during the ABSI consensus meetings are
presented in this paper.
PMID- 22047632
TI - Is Alzheimer's disease amyloidosis the result of a repair mechanism gone astray?
AB - Here, we synthesize several lines of evidence supporting the hypothesis that at
least one function of amyloid-beta is to serve as a part of the acute response to
brain hemodynamic disturbances intended to seal vascular leakage. Given the
resilient and adhesive physicochemical properties of amyloid, an abluminal
hemostatic repair system might be highly advantageous, if deployed on a limited
and short-term basis, in young individuals. However, in the aged, inevitable
cardiovascular dysfunction combined with brain microvascular lesions may yield
global chronic hypoperfusion that may lead to continuous amyloid deposition and
consequential negative effects on neuronal viability. A large body of
experimental evidence supports the hypothesis of an amyloid-beta rescue function
gone astray. Preventing or inducing the removal of amyloid in Alzheimer's disease
(AD) has been simultaneously successful and disappointing. Amyloid deposits
clearly play major roles in AD, but they may not represent the preeminent factor
in dementia pathogenesis. Successful application of AD preventative approaches
may hinge on an accurate and comprehensive view of comorbidities, including
cardiovascular disease, diabetes, and head trauma.
PMID- 22047633
TI - Effect of human cerebrospinal fluid sampling frequency on amyloid-beta levels.
AB - BACKGROUND: beta-amyloid peptide (Abeta) is associated with neurodegeneration in
Alzheimer's disease. Emerging evidence indicates that Abeta levels in
cerebrospinal fluid (CSF) may serve as an early clinical biomarker for evaluating
pharmacological activity of new drug candidates targeting Abeta production or
Abeta clearance. Therefore, it is critical to understand whether intrasubject
levels of CSF Abeta are consistent between sampling intervals to determine
whether Abeta can be used as a pharmacodynamic biomarker for drug candidates.
Previous studies have produced seemingly conflicting observations for the
intrasubject stability of CSF Abeta levels; we attempt to reconcile these
conflicting observations. METHODS: The current study examined the Abeta levels in
CSF collected with various sampling frequencies from three clinical studies
conducted in healthy young or elderly subjects at the same investigative site for
the purpose of designing future studies. RESULTS: The results suggest that CSF
sampling frequency and/or sampling volume contributes to intrasubject variability
in CSF Abeta levels, and that lowering the CSF sampling frequency may help
minimize this effect. CONCLUSION: These results will help guide clinical trial
design for Alzheimer's disease therapy.
PMID- 22047635
TI - Prognostic evaluation of tumour type and other histopathological characteristics
in advanced epithelial ovarian cancer, treated with surgery and
paclitaxel/carboplatin chemotherapy: cell type is the most useful prognostic
factor.
AB - AIM: Ovarian carcinomas have been classified into types I and II according to the
hypothesised mode of carcinogenesis and molecular characteristics. The prognostic
significance of this classification has not been studied. PATIENTS AND METHODS:
Five hundred and sixty-eight patients with histologically confirmed, ovarian,
fallopian tube or peritoneal carcinomas, international federation of gynecology
and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following
cytoreductive surgery, were included in this analysis. Type I included low-grade
serous, mucinous, endometrioid and clear-cell and type II high-grade serous,
unspecified adenocarcinomas and undifferentiated carcinomas. RESULTS: Median
overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576).
In contrast to type II, there was considerable prognostic heterogeneity among the
subtypes included in type I. Cox regression analysis showed that cell-type
classification: low-grade serous, mucinous, endometrioid, clear-cell, type II
(high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was
an independent predictor of survival (respective median OS 121 versus 15 versus
64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological
subtype or tumour type (I versus II) did not offer additional prognostic
information. CONCLUSION: The proposed model of ovarian tumourigenesis does not
reflect tumour behaviour in advanced disease. Tumour-cell type is the most
relevant histopathological prognostic factor in advanced ovarian cancer treated
with platinum/paclitaxel.
PMID- 22047636
TI - High prevalence of cervical squamous intraepithelial lesions in women on
antiretroviral therapy in Cameroon: Is targeted screening feasible?
AB - BACKGROUND: Cervical cancer is the most common cancer in women in low-income
countries. Although cervical cancer incidence and mortality is higher in HIV
positive women, resource limitations restrict the implementation of systematic
screening programs in these women. We explored the potential for targeted
screening by assessing the prevalence, severity and predictors of cervical
squamous intra-epithelial lesions (SILs) in HIV-positive women in Cameroon.
METHODS AND FINDINGS: We conducted a cross-sectional study of women on
antiretroviral therapy in Cameroon. Socio-demographic, behavioral, and clinical
information was obtained from eligible women. Cervical exfoliated cells were then
collected, a conventional cytology performed and epithelial lesions classified
according to the Bethesda 2001 system. A total of 282 women, aged 19-68 years,
were enrolled in this study. The median CD4 count was 179 cells/microliter
(interquartile range: 100-271). SILs were detected in 43.5% of the 276 women with
satisfactory samples: including atypical squamous cells of unknown significance
(ASCUS) 0.7%, low-grade SIL (LSIL) 25.0%, atypical squamous cells, cannot exclude
high grade lesions (ASC-H) 14.5%, and high-grade SIL (HSIL) 3.3%. None of the
demographic or clinical characteristics considered significantly predicted the
presence of any SILs or the presence of severe lesions requiring colposcopy.
CONCLUSION: The prevalence of SIL in women on antiretroviral therapy in Cameroon
was high underscoring the need for screening and care in this population. In the
absence of any accurate demographic or clinical predictor of SIL, targeted
screening does not seem feasible. Alternative affordable screening options need
to be explored.
PMID- 22047634
TI - The Alzheimer's Disease Neuroimaging Initiative: a review of papers published
since its inception.
AB - The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing,
longitudinal, multicenter study designed to develop clinical, imaging, genetic,
and biochemical biomarkers for the early detection and tracking of Alzheimer's
disease (AD). The study aimed to enroll 400 subjects with early mild cognitive
impairment (MCI), 200 subjects with early AD, and 200 normal control subjects;
$67 million funding was provided by both the public and private sectors,
including the National Institute on Aging, 13 pharmaceutical companies, and 2
foundations that provided support through the Foundation for the National
Institutes of Health. This article reviews all papers published since the
inception of the initiative and summarizes the results as of February 2011. The
major accomplishments of ADNI have been as follows: (1) the development of
standardized methods for clinical tests, magnetic resonance imaging (MRI),
positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a
multicenter setting; (2) elucidation of the patterns and rates of change of
imaging and CSF biomarker measurements in control subjects, MCI patients, and AD
patients. CSF biomarkers are consistent with disease trajectories predicted by
beta-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151-3) and tau
mediated neurodegeneration hypotheses for AD, whereas brain atrophy and
hypometabolism levels show predicted patterns but exhibit differing rates of
change depending on region and disease severity; (3) the assessment of
alternative methods of diagnostic categorization. Currently, the best classifiers
combine optimum features from multiple modalities, including MRI, [(18)F]
fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development
of methods for the early detection of AD. CSF biomarkers, beta-amyloid 42 and
tau, as well as amyloid PET may reflect the earliest steps in AD pathology in
mildly symptomatic or even nonsymptomatic subjects, and are leading candidates
for the detection of AD in its preclinical stages; (5) the improvement of
clinical trial efficiency through the identification of subjects most likely to
undergo imminent future clinical decline and the use of more sensitive outcome
measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally
predicted future decline better than other modalities, whereas MRI measures of
change were shown to be the most efficient outcome measures; (6) the confirmation
of the AD risk loci CLU, CR1, and PICALM and the identification of novel
candidate risk loci; (7) worldwide impact through the establishment of ADNI-like
programs in Europe, Asia, and Australia; (8) understanding the biology and
pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker
data with clinical data from ADNI to stimulate research that will resolve
controversies about competing hypotheses on the etiopathogenesis of AD, thereby
advancing efforts to find disease-modifying drugs for AD; and (9) the
establishment of infrastructure to allow sharing of all raw and processed data
without embargo to interested scientific investigators throughout the world. The
ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a
renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an
additional 550 participants.
PMID- 22047637
TI - The impact of significant others in motivational enhancement therapy: findings
from project MATCH.
AB - BACKGROUND: Social network support for abstinence has been associated with
improved treatment outcomes among samples of individuals with alcohol use
disorders. As a result, research studies have focused on the inclusion of
significant others (SOs) in the treatment process. Nonetheless, little is known
about 1) the specific influence SOs may have on clients during treatment sessions
or 2) whether SO within-session behaviors have any relationship to client post
treatment drinking. METHOD: In the current study, Motivational Enhancement
Therapy sessions in which a SO was present were coded using a behavioral coding
system designed to measure SO and client within-session language. RESULTS:
Relationships were observed between SO and client within-session language.
Furthermore, some specific SO categories of language predicted post-treatment
client drinking. CONCLUSIONS: This study is the first systematic evaluation of SO
contributions in substance abuse treatment sessions. Future research examining SO
language in the treatment of alcohol use disorders might allow clinicians to
avoid contributions from SOs that are associated with poorer drinking outcomes.
PMID- 22047638
TI - Differential accumulation of BPA in some tissues of offspring of Balb-C mice
exposed to different BPA doses.
AB - Pregnant adult Balb-C mice were exposed daily to two different doses of Bisphenol
A (BPA) by subcutaneous injection beginning on gestational day 1 through the
seventh day after delivery. The mothers were sacrificed on postpartum day 21, and
the offspring were sacrificed at 3 months of age. Control mice were subjected to
the same experimental protocol but received saline injections. The liver,
muscles, hindbrain and forebrain of the offspring were dissected and processed
using HPLC to assess the level of BPA in the tissues and to determine its
dependence on the exposure dose and gender. For comparison, the same tissues were
dissected from the mothers and analysed. We report the following results: (1) the
level of BPA that accumulated in a given tissue was dependent on the exposure
dose; (2) the rank order of BPA accumulation in the various tissues was dependent
on the gender of the offspring; (3) the average BPA concentrations in the liver
and muscle of the female offspring were higher than in the males; and (4) the
average BPA concentration in the central nervous system (i.e., the hindbrain and
forebrain) of the male offspring was higher than in the females.
PMID- 22047639
TI - Determination of pyrimidine and purine bases by reversed-phase capillary liquid
chromatography with at-line surface-enhanced Raman spectroscopic detection
employing a novel SERS substrate based on ZnS/CdSe silver-quantum dots.
AB - We have developed a new SERS substrate based on the reduction of silver nitrate
in the presence of ZnS-capped CdSe quantum dots. This substrate showed higher
sensitivities as compared to a hydroxylamine-reduced silver sol. On the basis of
this new substrate, at-line SERS detection was coupled with capillary liquid
chromatography (cap-LC) for the separation and selective determination of
pyrimidine and purine bases. For this purpose, wells of a dedicated microtiter
plate were loaded with 20 MUL of the SERS substrate and placed on an automated
x,y translation stage. A flow-through microdispenser capable of ejecting 50 pL
droplets, at a frequency 100 Hz, was used as the interface to connect the cap-LC
system to the wells loaded with SERS substrate. A detailed study of the
dependence of both the separation and the surface-enhanced Raman spectra of each
base on the pH was performed to optimize the system for maximum sensitivity and
selectivity. Highly satisfactory analytical figures of merit were obtained for
the six investigated bases (cytosine, xanthine, hypoxanthine, guanine, thymine,
and adenine) with detection limits ranging between 0.2 and 0.3 ng injected on the
capillary LC column, and the precisions were in the range of 3.0-6.3%.
PMID- 22047640
TI - Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis
in rheumatoid arthritis - a potential role for heat shock protein 70.
AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which
causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid
synovium has been attributed to abnormal apoptosis. While not comprehensively
investigated, perturbations in peripheral blood lymphocyte (PBL) apoptosis may
also be involved in perpetuation of autoimmune processes in RA. METHODS: We
investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by
monitoring the translocation of phosphatidylserine using the Annexin-V assay. To
examine the role of death receptor mediated apoptosis as well as activation
induced-cell-death (AICD), PBLs were labeled with CD95/Fas and CD69 markers and
enumerated by flow cytometry. Proteolytic activity of initiator and executioner
caspases was determined by luminometry. DNA fragmentation assays were used to
examine whether apoptotic signals were transduced to the nucleus. Quantitative
PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs.
Since heat-shock-protein-70 (HSP70) is an inducible protein which modulates
apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry
and western blots. RESULTS: The RA-PBLs showed signs of elevated apoptosis whilst
in circulation. These include increases in the loss of plasma membrane asymmetry,
indicated by increased externalization of phosphatidylserine (especially in B
lymphocytes). RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but
low levels of the CD69 marker suggested that this was not associated with immune
activation. Although downstream markers of apoptosis such as caspase-3/7
activity, were increased, no DNA fragmentation was observed in RA-PBLs.
Interestingly, elevated levels of apoptosis did not correlate with absolute
lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs
compared to controls. CONCLUSION: The results suggest that while apoptosis may be
initiated in RA-PBLs, they may lack commitment to fully executing the apoptotic
program. This may be related to inhibition on apoptotic transduction by HSP70.
This study provides evidence that abnormalities in RA-PBLs apoptosis may occur
whilst still in circulation and may contribute to pathogenesis of the disease.
PMID- 22047641
TI - Receptor-mediated endocytosis of nanoparticles of various shapes.
AB - Cellular uptake through endocytosis is crucial for drug delivery and
nanomedicine. However, the conditions under which passive endocytosis (i.e., not
ATP driven) takes place are not well understood. We report MD simulations of the
passive uptake of ligand-coated nanoparticles with varying size, shape, coverage,
and membrane-binding strength. We find that the efficiency of passive endocytosis
is higher for spherocylindrical particles than for spheres and that endocytosis
is suppressed for particles with sharp edges.
PMID- 22047642
TI - Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with
pyrazole ligands.
AB - Here we present the synthesis of the new Ni(II) complexes with chelating ligands
1-benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (a), 5-(2-hydroxyphenyl)-3-methyl-1
(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (b) and 1-benzothiazol-2
yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (c).
These ligands a-c create solid complexes with Ni(II). The crystal and molecular
structures of two complexes were determined by X-ray diffraction method. Thermal
stability of two complexes with ligand c by TG/DTG and DSC methods were also
shown. Cytotoxic activity of all the complexes against three tumour cell lines
and to normal endothelial cells (HUVEC) was also estimated. Complexes with ligand
c exhibited relatively high cytotoxic activity towards HL-60 and NALM-6 leukaemia
cells and WM-115 melanoma cells. Cytotoxic effectiveness of one of these
complexes against melanoma WM-115 cells was two times higher than that of
cisplatin. The protonation constant log K=9.63 of ligand b corresponding to the
phenol 2-hydroxy group has been determined in 10% (v/v) DMSO/water solution (25
degrees C). The coordination modes (formation of two monomeric species: NiL and
NiL(2)) in the complexes with Ni(II) are discussed for b on the basis of the
potentiometric and UV/Vis data.
PMID- 22047643
TI - Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of
its derivatives.
AB - We report herein the chemical synthesis and biological evaluation of beta
carboline alkaloid pityriacitrin and some of its new derivatives. Using
tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the
starting materials, pityriacitrin and some of its derivatives were synthesized
via the acid-catalyzed Pictet-Spengler reaction and fully characterized by (1)H
and (13)C NMR, mass spectroscopy and IR determinations. Biological studies
revealed that pityriacitrin has a weak antiproliferative activity against a panel
of breast and prostate cancer cell lines, whereas some of its derivatives
exhibited stronger and potent activity, which was associated with induction of
both cell apoptosis and necrosis.
PMID- 22047644
TI - Cyclin kinase subunit 1B nuclear expression predicts an adverse outcome for
patients with relapsed/refractory multiple myeloma treated with bortezomib.
AB - Amplification of cyclin kinase subunit 1B gene on chromosome 1q21 resulting in
overexpression of cyclin kinase subunit 1B has been associated with disease
progression in multiple myeloma. Bortezomib is a proteasome inhibitor that
induces apoptosis in various cancer cells and has been shown to be effective as a
salvage therapy for relapsed/refractory multiple myeloma. Our group has recently
reported the adverse effect of 1q21 gains in relapsed and refractory multiple
myeloma treated with bortezomib. However, whether nuclear cyclin kinase subunit
1B protein expression correlates with 1q21 gains and has prognostic value in
patients with multiple myeloma receiving bortezomib regimen remains unclear. We,
therefore, evaluated the nuclear expression of cyclin kinase subunit 1B protein
in patients with relapsed/refractory multiple myeloma undergoing bortezomib
therapy by immunohistochemistry. The 1q21 amplification status of the same cohort
was examined by interphase cytoplasmic immunoglobulin fluorescence in situ
hybridization. Of 60 cases, 19 (32%) were positive for cyclin kinase subunit 1B
nuclear expression by immunohistochemistry. Seventeen (89%) of the
immunohistochemistry-positive cases had 1q21 gain detected by cytoplasmic
immunoglobulin fluorescence in situ hybridization, and 17 (77%) of the 22 cases
with 1q21 gain showed increased cyclin kinase subunit 1B protein expression.
cyclin kinase subunit 1B expression and 1q21 gain were strongly correlated (P <
.0001). There was no significant difference in response rate between patients
with and without cyclin kinase subunit 1B nuclear expression. However, patients
with cyclin kinase subunit 1B expression had a significantly shorter progression
free survival (1.9 versus 5.6 months; P < .0001) and overall survival (4.9 versus
22.4 months; P = .012) compared with those without cyclin kinase subunit 1B
expression. Our results indicated that cyclin kinase subunit 1B nuclear
expression detected by immunohistochemistry is an adverse prognostic factor for
patients with multiple myeloma treated with bortezomib therapy.
PMID- 22047645
TI - Sarcoidosis does not belong to or overlap with immunoglobulin G4-related diseases
based on an assessment of serum immunoglobulin G4 levels in cardiac and
noncardiac sarcoidosis.
AB - Although sarcoidosis may exhibit histopathologic features similar to those of a
newly emerging clinical entity, immunoglobulin G4-related sclerosing disease,
sarcoidosis is currently not considered to be associated with immunoglobulin G4
related immunoinflammation. Not many studies on this association have been
reported. We investigated serum immunoglobulin G4 levels among patients with
sarcoidosis with or without cardiac involvement (cardiac sarcoidosis and non
cardiac sarcoidosis patients). The mean serum immunoglobulin G4 level among the
65 patients with sarcoidosis was 56.8 +/- 43.0 mg/dL, which did not significantly
differ between patients with cardiac sarcoidosis (54 +/- 48 mg/dL, n = 12) and
patients without cardiac sarcoidosis (58 +/- 42 mg/dL; n = 53). Serum level of
soluble interleukin 2 receptor, a potent marker that may reflect sarcoidosis
activity, was elevated in cardiac sarcoidosis (910 +/- 683 U/L) and noncardiac
sarcoidosis (689 +/- 399 U/L) but did not significantly differ between the
groups. Immunohistochemistry of cardiac or lymph node specimens from patients
with cardiac sarcoidosis showed only sparse or no infiltration of immunoglobulin
G4-positive lymphocytes, in contrast to the moderate to severe infiltration of
CD68-positive macrophages and CD45-positive lymphocytes. Although the number of
study subjects was small, these findings collectively suggest that regardless of
the presence or absence of cardiac involvement, sarcoidosis does not belong to or
overlap with immunoglobulin G4-related sclerosing disease.
PMID- 22047646
TI - The presence and location of epithelial implants and implants with epithelial
proliferation may predict a higher risk of recurrence in serous borderline
ovarian tumors: a clinicopathologic study of 188 cases.
AB - Serous borderline ovarian tumors have a favorable prognosis, and recurrences are
uncommon. The factors influencing recurrence are not fully understood. Epithelial
inclusions are identified in serous borderline ovarian tumors and are
traditionally referred to as epithelial implants, which often show epithelial
proliferation. We investigated whether the presence of epithelial implant and
epithelial proliferation portends a higher risk for recurrence of serous
borderline ovarian tumors in patients who underwent surgical removal of these
tumors. Also examined was whether the anatomical site of epithelial implant and
epithelial proliferation was associated with a higher risk of recurrence. One
hundred eighty-eight cases of pure serous or predominantly serous borderline
ovarian tumors were studied for the presence of epithelial implant and epithelial
proliferation, and subsequent recurrences were recorded. The anatomical sites of
epithelial implant and epithelial proliferation were compared between serous
borderline ovarian tumors with or without recurrence. Statistical analysis was
performed using the chi(2) test. Epithelial implant was noted in 106 cases (56%),
and epithelial proliferation, in 26 cases (14%). Recurrence was identified in
10.4% cases with epithelial implant and 23% cases with epithelial proliferation.
Statistical analyses of patients with recurrence showed significant differences
in the following groups: epithelial implant versus no epithelial implant (P <
.025) and epithelial proliferation versus no epithelial implant (P < .001).
Recurrence rates were higher in the epithelial implant and epithelial
proliferation groups as compared with no epithelial implant or epithelial
proliferation groups. Epithelial implant and epithelial proliferation appear to
pose a statistically significantly higher risk of recurrence in serous borderline
ovarian tumors as compared with the absence of epithelial implant. Although the
anatomical location of such implants was not significantly associated with a
higher risk, the presence of epithelial proliferation at multiple sites was more
frequently seen in recurrent serous borderline ovarian tumors.
PMID- 22047647
TI - Expression of endothelin 2 and localized clear cell renal cell carcinoma.
AB - Despite the rising incidence of clear cell renal cell carcinoma, the molecular
events that support its development and progression remain unclear. Herein, we
evaluate the association of endothelin 2 expression with both clear cell renal
cell carcinoma development and progression-free survival. We conducted real-time
polymerase chain reaction to determine endothelin 2 expression levels on 238
patients who underwent nephrectomy for localized clear cell renal cell carcinoma,
161 of whom also had adjacent normal kidney samples available for analysis. To
evaluate associations with clear cell renal cell carcinoma development, linear
mixed models were used to compare differential expression between tumor and a
normal kidney as well as to explore interactions with clinicopathologic features.
To evaluate associations with prognosis, Cox proportional hazards models were
used to assess the association of progression-free survival and endothelin 2
expression in tumor tissue. Overall, endothelin 2 expression was higher in tumor
samples versus patient-matched normal kidney samples, with an average fold change
of 1.99 (95% confidence interval, 1.48-2.60; P < .0001). This overexpression in
tumor versus normal kidney samples was more pronounced in low- compared with high
grade tumors (interaction, P = .0002), in early- compared with late-stage tumors
(interaction, P = .001), and in tumors without compared with those with necrosis
(interaction, P = .001). Moreover, an increasing endothelin 2 expression in
tumors was associated with a longer progression-free survival (hazard ratio,
0.89; 95% confidence interval, 0.80-0.99; P = .03); however, after controlling
for known clinicopathologic factors, this association was attenuated (hazard
ratio, 0.99; 95% confidence interval, 0.89-1.09; P = .7). Up-regulation of
endothelin 2 is a common and early event in localized clear cell renal cell
carcinoma. Higher tumor expression of endothelin 2 is associated with a longer
progression-free survival but not after adjustment for well-known pathologic
indices. Thus, although endothelin 2 does not appear to be an independent
prognostic marker, there is evidence of a putative role in clear cell renal cell
carcinoma progression. If supportive mechanistic data can be produced, endothelin
2 could represent a potential target for chemopreventive or neoadjuvant
therapeutics for clear cell renal cell carcinoma.
PMID- 22047648
TI - Implementing clinical trials on an international platform: challenges and
perspectives.
AB - The importance of conducting medical research on a global or international
platform cannot be overemphasized in current times. Sponsors are encouraging
international clinical trials for a number of reasons. Globally, clinical trials
are under increasing pressure to meet patient recruitment goals quickly and
efficiently, at times with very limited resources. Conducting clinical trials in
multiple countries increases access to potentially eligible study subjects. It is
reasonable to believe that international trials will be completed more quickly
and efficiently, leading to more rapid advancement in science and conservation of
research-specific resources. Rapid advancement in science can reduce the burden
of disease, promote health, and extend longevity for all people. In addition,
generalizability, one of the major goals of translational medicine, will increase
when recruiting patients from multiple countries and multiple ethnicities.
Further, improvement of global health may be possible when certain types of
clinical trials are conducted in countries that would not otherwise have access
to an innovative drug or intervention.
PMID- 22047649
TI - Surgical treatment of brain metastasis: a review.
AB - Brain metastasis is the most common intracranial tumor in adults. Currently,
treatment of brain metastasis requires multidisciplinary approach tailored for
each individual patient. Surgery has an indispensible role in relieving
intracranial mass effect, improving neurological status and survival while
providing or confirming neuropathological diagnosis with low mortality and
morbidity rates. Besides the resection of a single brain metastasis in patients
with accessible lesions, good functional status, and absent/controlled
extracranial disease; surgery is proven to play a role in management of multiple
metastases. Surgical technique has an impact on the outcome since piecemeal
resection rather than en bloc resection and leaving infiltrative zone behind
around resection cavity may have a negative influence on local control. Best
local control of brain metastasis can be accomplished with optimal surgical
resection involving current armamentarium of preoperative structural and
functional imaging, intraoperative neuromonitoring, and advanced
microneurosurgical techniques; followed by adjunct therapies like stereotactic
radiosurgery, whole brain radiotherapy, or intracavitary therapies. Here,
treatment options for brain metastasis are discussed with controversies about
surgery.
PMID- 22047650
TI - CNS lymphoma masquerading as hemorrhagic stroke.
PMID- 22047651
TI - Anti-NMDAR encephalitis in small-cell lung cancer: a case report.
PMID- 22047652
TI - Anxiety sensitivity and breath-holding duration in relation to PTSD symptom
severity among trauma exposed adults.
AB - The present investigation examined the main and interactive effects of anxiety
sensitivity and behavioral distress tolerance, indexed using the breath-holding
task, in relation to PTSD symptom severity among trauma-exposed adults.
Participants were 88 adults (63.6% women; M(age)=22.9, SD=9.1, range=18-62),
recruited from the community, who met DSM-IV-TR PTSD Criterion A for lifetime
trauma exposure. Covariates included number of potentially traumatic events,
nonclinical panic attack history, and participant sex. Anxiety sensitivity was
significantly incrementally associated with PTSD total symptom severity, as well
as Avoidance and Hyperarousal symptom severity (p's<.01). Breath-holding duration
was not significantly related to PTSD symptom severity (p's>.05). However, breath
holding duration emerged as a significant moderator of the association between
anxiety sensitivity and PTSD Avoidance symptom severity, such that lower breath
holding duration exacerbated the effect of heightened anxiety sensitivity with
regard to PTSD Avoidance symptom severity.
PMID- 22047653
TI - Marginal benefit incidence of public health spending: evidence from Indonesian
sub-national data.
AB - We examine the marginal effects of decentralized public health spending by
incorporating estimates of behavioural responses to changes in health spending in
benefit incidence analysis. The analysis is based on a panel dataset of 207
Indonesian districts over the period from 2001 to 2004. We show that district
public health spending is largely driven by central government transfers, with an
elasticity of around 0.9. We find a positive effect of public health spending on
utilization of outpatient care in the public sector for the poorest two
quartiles. We find no evidence that public expenditures crowd out utilization of
private services or household health spending. Our analysis suggests that
increased public health spending improves targeting to the poor, as behavioural
changes in public health care utilization are pro-poor. Nonetheless, most of the
benefits of the additional spending accrued to existing users of services, as
initial utilization shares outweigh the behavioural responses.
PMID- 22047654
TI - Bacterial community structure and enzyme activities in a membrane bioreactor
(MBR) using pure oxygen as an aeration source.
AB - A pilot-scale membrane bioreactor was used to treat urban wastewater using pure
oxygen instead of air as a source of aeration, to study its influence on
bacterial diversity and levels of enzyme activities (acid and alkaline
phosphatases, glucosidase, protease, and esterase) in the sludge. The
experimental work was developed in two stages influenced by seasonal temperature.
Operational parameters (temperature, pH, BOD5, COD, total and volatile suspended
solids) were daily monitored, and enzyme activities measured twice a week.
Redundancy analysis (RDA) was used to reveal relationships between the level of
enzyme activities and the variation of operational parameters, demonstrating a
significant effect of temperature and volatile suspended solids. Bacterial
diversity was analyzed by temperature-gradient gel electrophoresis of PCR
amplified partial 16S rRNA genes. Significant differences in community structure
were observed between both stages. Sequence analysis revealed that the prevalent
Bacteria populations were evolutively close to Alphaproteobacteria (44%),
Betaproteobacteria (25%) and Firmicutes (17%).
PMID- 22047655
TI - Low temperature thermo-chemical pretreatment of dairy waste activated sludge for
anaerobic digestion process.
AB - An investigation into the influence of low temperature thermo-chemical
pretreatment on sludge reduction in a semi-continuous anaerobic reactor was
performed. Firstly, effect of sludge pretreatment was evaluated by COD
solubilization, suspended solids reduction and biogas production. At optimized
condition (60 degrees C with pH 12), COD solubilization, suspended solids,
reduction and biogas production was 23%, 22% and 51% higher than the control,
respectively. Secondly, semi-continuous process performance was studied in a lab
scale semi-continuous anaerobic reactor (5 L), with 4 L working volume. With
three operated SRTs, the SRT of 15 days was found to be most appropriate for
economic operation of the reactor. Combining pretreatment with anaerobic
digestion led to 80.5%, 117% and 90.4% of TS, SS and VS reduction respectively,
with an improvement of 103% in biogas production. Thus, low temperature thermo
chemical can play an important role in reducing sludge production.
PMID- 22047656
TI - Production and characterization of biopolyols and polyurethane foams from crude
glycerol based liquefaction of soybean straw.
AB - The feasibility of using crude glycerol to liquefy soybean straw for the
production of biopolyols and polyurethane (PU) foams was investigated in this
study. Liquefaction conditions of 240 degrees C, >180 min, 3% sulfuric acid
loading, and 10-15% biomass loading were preferred for the production of
biopolyols with promising material properties. Biopolyols produced under
preferential conditions showed hydroxyl numbers from 440 to 540 mg KOH/g, acid
numbers below 5 mg KOH/g, and viscosities from 16 to 45 Pa.s. PU foams produced
under preferential conditions showed densities from 0.033 to 0.037 g/cm3 and
compressive strength from 148 to 227 kPa. These results suggest that crude
glycerol can be used as an alternative solvent for the liquefaction of
lignocellulosic biomass such as soybean straw for the production of biopolyols
and PU foams. The produced biopolyols and PU foams showed material properties
comparable to their analogs from petroleum solvent based liquefaction processes.
PMID- 22047657
TI - Effects of nitrate on methane production, fermentation, and microbial populations
in in vitro ruminal cultures.
AB - The objective of this study was to examine the effects of nitrate on methane
production, important fermentation characteristics, Fibrobacter succinogenes,
Ruminococcus albus, Ruminococcus flavefaciens, total bacteria, and methanogens
using in vitro ruminal cultures. Potential adaptation of the above microbes and
persistency of nitrate to mitigate CH4 production were also evaluated. Methane
production was reduced by 70% at 12 MUmol ml(-1) and nearly completely at >=24
MUmol ml(-1) nitrate. Production of volatile fatty acids (VFAs) was affected to
different extents at different nitrate concentrations. Over a series of six
consecutive cultures receiving 12 MUmol ml(-1) nitrate, production of CH4 and VFA
did not change significantly. R. albus and R. flavefaciens seemed to adapt to
nitrate, while F. succinogenes and methanogens did not. Nitrate may be used in
achieving persistent mitigation of CH4 production by ruminants.
PMID- 22047658
TI - Improved volatile fatty acids production from proteins of sewage sludge with
anthraquinone-2,6-disulfonate (AQDS) under anaerobic condition.
AB - Organic matters in sewage sludge can be converted into volatile fatty acids
(VFAs) as renewable carbon sources. This work for the first time applied
anthraquinone-2,6-disulfonate (AQDS) for enhancing VFA production from sewage
sludge. With 0.066 or 0.33 g AQDS g(-1) dried solids (DS), the yields for VFAs
peak at 403 or 563 mg l(-1), 1.9- or 2.7-fold to the control. The accumulated
VFAs were principally composed of acetate and propionate. The AQDS enhances
degradation rates of model proteins (bovine serum albumin), but had little
enhancement on that of model polysaccharides (dextrans). The acidification step
is proposed the rate-limiting step for VFA production from sewage sludge, in
which the AQDS molecules shuttle electrons to accelerate the redox reactions
associated with amino acid degradation. Methanogenic activities are inhibited in
the presence of AQDS. The AQDS-assisted VFAs are renewable organic carbon
sources, although their direct use for anaerobic digestion is not advised.
PMID- 22047659
TI - Preparation of levoglucosenone through sulfuric acid promoted pyrolysis of
bagasse at low temperature.
AB - Fast pyrolysis of bagasse pretreated by sulfuric acid was conducted in a fixed
bed reactor to prepare levoglucosenone (LGO), a very important anhydrosugar for
organic synthesis. The liquid yield and LGO yield were studied at temperatures
from 240 to 350 degrees C and sulfuric acid loadings from 0.92 to 7.10 wt.%. An
optimal LGO yield of 7.58 wt.% was obtained at 270 degrees C with a sulfuric
acid pretreatment concentration of 0.05 M (corresponding to 4.28 wt.% sulfuric
acid loading). For comparison, microcrystalline cellulose pretreated by 0.05 M
sulfuric acid solution was pyrolyzed at temperature from 270 degrees C to 320
degrees C, and bagasse loaded with 3-5 wt.% phosphoric acid was pyrolyzed at
temperature from 270 degrees C to 350 degrees C. The highest yield of LGO from
bagasse was 30% higher than that from microcrystalline cellulose, and treatment
with sulfuric acid allowed a 21% higher yield than treatment with phosphoric
acid.
PMID- 22047660
TI - The lignin present in steam pretreated softwood binds enzymes and limits
cellulose accessibility.
AB - The influence of cellulose accessibility and protein loading on the efficiency of
enzymatic hydrolysis of steam pretreated Douglas-fir was assessed. It was
apparent that the lignin component significantly influences the
swelling/accessibility of cellulose as at low protein loadings (5FPU/g
cellulose), only 16% of the cellulose present in the steam pretreated softwood
was hydrolyzed while almost complete hydrolysis was achieved with the delignified
substrate. When lignin (isolated from steam pretreated Douglas-fir) was added
back in the same proportions it was originally found to the highly accessible and
swollen, delignified steam pretreated softwood and to a cellulose control such as
Avicel, the hydrolysis yields decreased by 9 and 46%, respectively. However, when
higher enzyme loadings were employed, the greater availability of the enzyme
could overcome the limitations imposed by both the lignin's restrictions on
cellulose accessibility and direct binding of the enzymes, resulting in a near
complete hydrolysis of the cellulose.
PMID- 22047661
TI - Enhanced enzymatic saccharification of kenaf powder after ultrasonic pretreatment
in ionic liquids at room temperature.
AB - This study demonstrates for the first time that the enzymatic hydrolysis of
cellulose is drastically enhanced following ultrasonic pretreatment of
lignocellulosic material in ionic liquids (ILs) when compared to conventional
thermal pretreatment. Five types of ILs, 1-buthyl-3-methylimidazolium chloride
(BmimCl), 1-allyl-3-methylimidazolium chloride (AmimCl), 1-ethyl-3
methylimidazolium chloride (EmimCl), 1-ethyl-3-methylimidazolium diethyl
phosphate (EmimDep), and 1-ethyl-3-methylimidazolium acetate (EmimOAc) were
tested. Cellulose saccharification ratio was about 20% for kenaf powders
pretreated in BmimCl, AmimCl, EmimCl, and EmimDep by conventional heating at 110
degrees C for 120 min. Conversely, 60-95% of cellulose was hydrolyzed to glucose,
subsequent to ultrasonic pretreatment in the same ILs for 120 min at 25 degrees
C. The cellulose saccharification ratio of kenaf powder in EmimOAc was 86% after
only 15 min of the ultrasonic pretreatment at 25 degrees C, compared to only 47%
in that case of thermal pretreatment in the IL.
PMID- 22047662
TI - Characterization of Phragmites cummunis rhizosphere bacterial communities and
metabolic products during the two stage sequential treatment of post methanated
distillery effluent by bacteria and wetland plants.
AB - This study deals with the characterization of rhizosphere bacterial communities
and metabolic products produced during the two stage sequential treatment of post
methanated distillery effluent by bacteria and constructed wetland plants.
Results showed that bacterial treatment followed by wetland plants (Phragmites
cummunis) resulted 94.5% and 96.0% reduction in BOD and COD values, respectively.
The PCR-RFLP analysis showed the presence of Stenotrophomonas, Enterobacter,
Pantoea, Acinetobacter and Klebsiella sp., as dominant rhizosphere bacterial
communities which play an important role in degradation and decolorization of
PMDE in wetland treatment system. Further, the LC-MS-MS and other
spectrophotometric analysis have shown that most of the pollutants detected in
untreated PMDE were diminished from bacteria and wetland plant treated PMDE
indicating that bacteria and wetland plant rhizosphere microbes utilized them as
carbon, nitrogen and energy source. While, methylbenzene, furfuryl alcohol, and 4
vinyl-2-methoxyphenol were detected as metabolites in bacteria and hexadecanol in
wetland plant rhizosphere treated PMDE.
PMID- 22047663
TI - Prognostic value of beta-human chorionic gonadotropin is dependent on day of
embryo transfer during in vitro fertilization.
AB - OBJECTIVE: To determine threshold beta-hCG levels predictive of an ongoing
pregnancy (OP), live birth (LB), and multiple gestation (MG) in IVF cycles
resulting from day-3 (D3) vs. day-5 (D5) embryo transfers (ET), to compare IVF
cycle characteristics and pregnancy outcomes in D3 vs. D5 ET groups, and to
assess the degree to which maternal characteristics and cycle parameters were
predictive of higher beta-hCG levels. DESIGN: Retrospective analysis. SETTING:
Infertility center. PATIENT(S): Women who had ET performed for IVF cycles between
July 2004 and January 2010. INTERVENTION(S): Embryo transfer performed on either
D3 or D5 after oocyte fertilization. MAIN OUTCOME MEASURE(S): Beta-hCG on day 15
after oocyte fertilization. RESULT(S): Beta-hCG levels were significantly higher
with D5 ET compared with D3 ETs (D3: 103.6 +/- 4.4 IU/L vs. D5: 198.0 +/- 10.6
IU/L), and a multivariate analysis demonstrated that D5 ET was a significant
predictor of higher beta-hCG levels. The beta-hCG thresholds predictive of OP
were 78 IU/L and 160 IU/L for D3 and D5 ET, which predicted OP in 96% and 91% of
cases, respectively. Similarly, for LB, the beta-hCG thresholds were 94 IU/L (79%
positive predictive value [PPV]) and 160 IU/L (88% PPV), and for MG were 250 IU/L
(18% PPV) and 316 IU/L (34% PPV), respectively. CONCLUSION(S): Initial beta-hCG
levels are dependent on the day of ET and are a reliable and highly predictive
tool for OP outcomes.
PMID- 22047664
TI - Intrauterine injection of human chorionic gonadotropin before embryo transfer
significantly improves the implantation and pregnancy rates in in vitro
fertilization/intracytoplasmic sperm injection: a prospective randomized study.
AB - OBJECTIVE: To investigate the value of intrauterine injection of human chorionic
gonadotropin (hCG) before embryo transfer (ET). DESIGN: Prospective randomized
study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Infertility patients
younger than 40 years undergoing their first in vitro
fertilization/intracytoplasmic sperm injection (IVF-ICSI). INTERVENTION(S): The
study group (n = 167) received either 100 IU of hCG (n = 83), or 200 IU of hCG (n
= 84) via intrauterine administration before ET. The control group (n = 93)
underwent ET without hCG. After the interim analysis, the modified study group (n
= 107) received intrauterine injection of 500 IU of hCG, and the control group (n
= 105) underwent ET without hCG. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate
(PR) and implantation rate (IR). RESULT(S): The IR and PR were statistically
significantly higher in the 500 hCG group (41.6% and 75%, respectively) as
compared with the control group (29.5% and 60%, respectively). The IR and PR were
26.6% and 54% in the 100 hCG group, 28.3% and 57% in the 200 IU hCG group, and
29.4% and 60% in the control group, respectively, with no statistically
significant difference. CONCLUSION(S): Intrauterine injection of 500 IU of hCG
before ET statistically significantly improved the implantation and pregnancy
rates in IVF/ICSI. CLINICAL TRIALS.GOV NUMBER: NCT 01030393.
PMID- 22047665
TI - Seminal leukocytes are Good Samaritans for spermatozoa.
AB - OBJECTIVE: To assess the effect of leukocytospermia on assisted reproductive
technology outcomes. DESIGN: Retrospective analysis. SETTING: University
laboratory. PATIENT(S): Couples attending the infertiliy clinic and involved in
ART program for IVF or ICSI. INTERVENTION(S): During a 7-year follow-up in an
assisted reproductive technology program, leukocytospermia was routinely
determined using the peroxidase technique. Donor sperm were excluded from the
study. MAIN OUTCOME MEASURE(S): Egg retrievals (N = 3,508) were distributed in 3
groups according to the leukocyte levels in semen from which fertilizing sperm
were extracted: group 1, absence of leukocytes (n = 3,026); group 2, moderate
leukocytospermia (<10(6)/mL) (n = 344); or group 3, high leukocytospermia
(>=10(6)/mL) (n = 138). They resulted in 1,463 IVF and 2,045 intracytoplasmic
sperm injection procedures that gave 802 clinical pregnancies. RESULT(S):
Surprisingly, the fertilization rate, cleavage rate, clinical pregnancy rate,
gestational age, and mean infant weight were significantly improved when seminal
leukocytes were present, regardless of the technique used. The only negative side
effects associated with a high level of seminal leukocytes (group 3) were an
elevated rate of early pregnancy loss (from 26.6% to 40.5%) and a 3-fold increase
in the percentage of ectopic pregnancies. CONCLUSION(S): At moderate levels
(<10(6)/mL), leukocytospermia appears to be physiologic. It is associated with
improved sperm fertilization ability and pregnancy outcome. At higher
concentrations, leukocytospermia alters neither sperm fertilization ability nor
the probability of clinical pregnancy when compared with nonleukocytic patients
with infertility. However, the pregnancy outcome is reduced.
PMID- 22047666
TI - Mutations in PMCA2 and hereditary deafness: a molecular analysis of the pump
defect.
AB - The inner ear converts sound waves into hearing signals through the
mechanoelectrical transduction (MET) process. Deflection of the stereocilia
bundle of hair cells causes the opening of channels that allow the entry of
endolymph K(+) and Ca(2+). Ca(2+) that enters is crucial to the hearing process
and is exported to the endolymph by the plasma membrane Ca(2+) pump (isoform
PMCA2w/a): disturbances of the balance between Ca(2+) penetration and ejection,
e.g. by pump mutations, generate deafness. Hearing loss caused by PMCA defects is
frequently exacerbated by mutations in cadherin 23, a single pass stereociliar
Ca(2+) binding protein that forms the tip links which permit the deflection of
the stereocilia bundle and thus the opening of the MET channels. The PMCA2w/a
pump ejects Ca(2+) to the endolymph even in the absence of the natural activator
calmodulin. This satisfies the special Ca(2+) homeostasis requirements of the
stereocilia/endolymph system. Here we have analyzed a mice and a human previously
described pump mutant. The human mutant only exacerbated the deafness produced by
a cadherin 23 mutation. The murine mutant overexpressed in model cells displayed
an evident defect both in the basal activity of the pump and in the long range
ejection of Ca(2+), the human mutant instead failed to impair the Ca(2+) ejection
by the pump.
PMID- 22047667
TI - [Drug prescriptions and demographic indicators in a diabetic population in
Argentina].
AB - OBJECTIVE: To analyse prescription patterns for antihyperglycemic drugs and co
medication in a group of diabetic patients regarding demographic variables.
METHOD: Observational, cross-sectional study performed from the prescriptions of
diabetic patients who attended a public health service in Argentina during 2008
2009. The programme Epidat 3.1 was used for statistical analysis. RESULTS: We
included 813 patients, among which 455 (56%) were women. There was a greater
prevalence of women under 40 years old (OR: 1.64; 95% CI: 1.05-2.56). Sixty-six
point seven percent (n=542) of the population used at least one drug acting on
the cardiovascular system, finding a positive statistical association between
frequency of use and age (P<.00001). CONCLUSIONS: We found that there was a
higher prevalence of women than men with early onset of type 2 diabetes mellitus.
There were no differences between the sexes regarding frequency of use of drugs
for the cardiovascular system.
PMID- 22047668
TI - Elevated plasma corticosterone increases metabolic rate in a terrestrial
salamander.
AB - Plasma glucocorticoid hormones (GCs) increase intermediary metabolism, which may
be reflected in whole-animal metabolic rate. Studies in fish, birds, and reptiles
have shown that GCs may alter whole-animal energy expenditure, but results are
conflicting and often involve GC levels that are not physiologically relevant. A
previous study in red-legged salamanders found that male courtship pheromone
increased plasma corticosterone (CORT; the primary GC in amphibians)
concentrations in males, which could elevate metabolic processes to sustain
courtship behaviors. To understand the possible metabolic effect of elevated
plasma CORT, we measured the effects of male courtship pheromone and exogenous
application of CORT on oxygen consumption in male red-legged salamanders
(Plethodon shermani). Exogenous application of CORT elevated plasma CORT to
physiologically relevant levels. Compared to treatment with male courtship
pheromone and vehicle, treatment with CORT increased oxygen consumption rates for
several hours after treatment, resulting in 12% more oxygen consumed (equivalent
to 0.33 J) during our first 2h sampling period. Contrary to our previous work,
treatment with pheromone did not increase plasma CORT, perhaps because subjects
used in this study were not in breeding condition. Pheromone application did not
affect respiration rates. Our study is one of the few to evaluate the influence
of physiologically relevant elevations in CORT on whole-animal metabolism in
vertebrates, and the first to show that elevated plasma CORT increases metabolism
in an amphibian.
PMID- 22047669
TI - Assessing therapeutic competence in cognitive therapy for social phobia:
psychometric properties of the cognitive therapy competence scale for social
phobia (CTCS-SP).
AB - BACKGROUND: There has been considerable acknowledgement in treatment outcome
research that, although the assessment of treatment integrity is essential in
many respects, it requires great effort as well as resources and is therefore
often neglected. AIMS: In order to fill this gap, the Cognitive Therapy
Competence Scale for Social Phobia (CTCS-SP) was developed, based on the
Cognitive Therapy Scale, to measure therapist competence in delivering cognitive
therapy for social phobia. The aim of the present study was to investigate
interrater reliability, internal consistency and retest reliability of the scale.
METHOD: Raters evaluated therapist competence from 161 videotaped sessions (98
patients) selected from 234 cognitive treatments within a multi-centre study.
RESULTS: Interrater-reliability was found to be high for the overall score (ICC =
.81) and moderate for individual items (ICC = .62-.92). Internal consistency and
retest reliability were also found to be high (Cronbach's alpha = .89; (ICCretest
= .86). CONCLUSIONS: The results indicate that the CTCS-SP is highly reliable. As
even individual items yield satisfactory reliability, the scale can be used in
various fields of research, including the measurement of changes in skill
acquisition and the impact of competence on outcome criteria.
PMID- 22047670
TI - Effects of a radiation dose reduction strategy for computed tomography in
severely injured trauma patients in the emergency department: an observational
study.
AB - BACKGROUND: Severely injured trauma patients are exposed to clinically
significant radiation doses from computed tomography (CT) imaging in the
emergency department. Moreover, this radiation exposure is associated with an
increased risk of cancer. The purpose of this study was to determine some effects
of a radiation dose reduction strategy for CT in severely injured trauma patients
in the emergency department. METHODS: We implemented the radiation dose reduction
strategy in May 2009. A prospective observational study design was used to
collect data from patients who met the inclusion criteria during this one year
study (intervention group) from May 2009 to April 2010. The prospective data were
compared with data collected retrospectively for one year prior to the
implementation of the radiation dose reduction strategy (control group). By
comparison of the cumulative effective dose and the number of CT examinations in
the two groups, we evaluated effects of a radiation dose reduction strategy. All
the patients met the institutional adult trauma team activation criteria. The
radiation doses calculated by the CT scanner were converted to effective doses by
multiplication by a conversion coefficient. RESULTS: A total of 118 patients were
included in this study. Among them, 33 were admitted before May 2009 (control
group), and 85 were admitted after May 2009 (intervention group). There were no
significant differences between the two groups regarding baseline
characteristics, such as injury severity and mortality. Additionally, there was
no difference between the two groups in the mean number of total CT examinations
per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective
dose of the total CT examinations per patient significantly decreased from 78.71
mSv to 29.50 mSv (p < 0.001). CONCLUSIONS: The radiation dose reduction strategy
for CT in severely injured trauma patients effectively decreased the cumulative
effective dose of the total CT examinations in the emergency department. But not
effectively decreased the number of CT examinations.
PMID- 22047671
TI - Neural regulation of the immune system modulates hypertension-induced target
organ damage.
AB - Innate and acquired immune mechanisms are involved in hypertension-induced target
organ damage. Immunosuppressive treatments directed at T lymphocytes, NF-kappaB
activation, or tumor necrosis factor-alpha production are all successful in
ameliorating cardiac or renal injury. Recently, important modulatory functions
involving the autonomic nervous system have been uncovered. Involved are an
afferent detection arm that sends vagal-mediated signals to the brain and an
efferent arm that includes the spleen and important nicotinic acetylcholine
receptor subunit. The signaling attenuates inflammatory activity. Splenectomy or
operations that injure the vagus or splenic abrogate these important protective
mechanisms. Vagal stimulation, either electrical or pharmacological, could
provide additional protection. The field of neuroimmunology will become
increasingly important to cardiovascular clinicians.
PMID- 22047672
TI - Stand-off spatial offset Raman spectroscopy for the detection of concealed
content in distant objects.
AB - A pulsed (4.4 ns pulse length) frequency-doubled Nd:YAG laser operated at 10 Hz
was used to generate Raman scattering of samples at a distance of 12 m. The
scattered light was collected by a 6 in. telescope, and the Raman spectrum was
recorded using an Acton SP-2750 spectrograph coupled to a gated intensified
charge-coupled device (ICCD) detector. Applying a spatial offset between the
point where the laser hit the sample and the focus of the telescope on the sample
enabled collection of Raman photons that were predominantly generated inside the
sample and not from its surface. This is especially effective when the content of
concealed objects should be analyzed. High-quality Raman spectra could be
recorded, within 10 s of data acquisition, from a solid (NaClO(3)) as well as a
liquid (isopropyl alcohol) placed inside a 1.5 mm thick opaque low-density
polyethylene (LDPE) plastic bottle. The applied spatial offset was also
advantageous in cases where the surface of the container was highly fluorescent.
In such a situation, Raman spectra of the sample could not be recorded when the
sampling volume (telescope observation field) coincided with the focus of the
excitation laser. However, with the use of a spatial offset of some millimeters,
a clear Raman spectrum of the content (isopropyl alcohol) in a strongly
fluorescent plastic container was obtained.
PMID- 22047673
TI - A geometric morphometric analysis of hominin upper premolars. Shape variation and
morphological integration.
AB - This paper continues the series of articles initiated in 2006 that analyse
hominin dental crown morphology by means of geometric morphometric techniques.
The detailed study of both upper premolar occlusal morphologies in a
comprehensive sample of hominin fossils, including those coming from the Gran
Dolina-TD6 and Sima de los Huesos sites from Atapuerca, Spain, complement
previous works on lower first and second premolars and upper first molars. A
morphological gradient consisting of the change from asymmetric to symmetric
upper premolars and a marked reduction of the lingual cusp in recent Homo species
has been observed in both premolars. Although percentages of correct
classification based on upper premolar morphologies are not very high,
significant morphological differences between Neanderthals (and European middle
Pleistocene fossils) and modern humans have been identified, especially in upper
second premolars. The study of morphological integration between premolar
morphologies reveals significant correlations that are weaker between upper
premolars than between lower ones and significant correlations between
antagonists. These results have important implications for understanding the
genetic and functional factors underlying dental phenotypic variation and
covariation.
PMID- 22047680
TI - Mental incapacity in hospitalised patients undergoing percutaneous endoscopic
gastrostomy insertion.
AB - BACKGROUND & AIMS: Decisions to insert percutaneous endoscopic gastrostomy (PEG)
tubes may be difficult because patients have serious underlying disease, and the
procedure has associated risks. Patients may also lack mental capacity to consent
to PEG insertion. This study aimed to prospectively determine the prevalence of
mental incapacity in hospitalised patients undergoing PEG insertion. METHODS:
Mental capacity was assessed using the MacArthur Competence Assessment Tool for
Treatment (MacCAT-T) in 72 consecutive inpatients referred for PEG insertion.
Cognitive function was measured using the Mini-Mental State Examination (MMSE).
Sixty eight inpatients and 69 outpatients having diagnostic upper
gastrointestinal (UGI) endoscopy were similarly studied. RESULTS: Thirty nine of
the PEG patients had suffered stroke, and none had a primary diagnosis of
dementia. Seventy four % (53/72) of inpatients referred for PEG, 22% (15/68) of
inpatients having UGI endoscopy, and 3% (2/69) of outpatients having UGI
endoscopy, lacked mental capacity, p < 0.001. MMSE scores were normal in just 18%
of inpatients having PEG, in 72% of inpatients having UGI endoscopy, and in 91%
of outpatients having UGI endoscopy, p < 0.001. CONCLUSION: Amongst inpatients
undergoing PEG insertion there is a high prevalence (three-quarters patients) of
mental incapacity to consent to this important intervention. Decisions have to be
made on behalf of most inpatients referred for PEG insertion.
PMID- 22047681
TI - Randomized phase III clinical trial of a combined treatment with carnitine +
celecoxib +/- megestrol acetate for patients with cancer-related
anorexia/cachexia syndrome.
AB - BACKGROUND & AIMS: A phase III, randomized non-inferiority study was carried out
to compare a two-drug combination (including nutraceuticals, i.e. antioxidants)
with carnitine + celecoxib +/- megestrol acetate for the treatment of cancer
related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of
lean body mass (LBM) and improvement of total daily physical activity. Secondary
endpoint was: increase of physical performance tested by grip strength and 6-min
walk test. METHODS: Sixty eligible patients were randomly assigned to: arm 1, L
carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day +
celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients
received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day,
carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months.
Planned sample size was 60 patients. RESULTS: The results did not show a
significant difference between tre atment arms in both primary and secondary
endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X
ray absorptiometry and by L3 computed tomography) increased significantly in both
arms as well as physical performance assessed by 6MWT. Toxicity was quite
negligible and comparable between arms. CONCLUSIONS: The results of the present
study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug
combination + megestrol acetate). Therefore, this simple, feasible, effective,
safe, low cost with favorable cost-benefit profile, two-drug approach could be
suggested in the clinical practice to implement CACS treatment.
PMID- 22047682
TI - A revertible, autonomous, self-assembled DNA-origami nanoactuator.
AB - A DNA-origami actuator capable of autonomous internal motion in accord to an
external chemical signal was designed, built, operated and imaged. The functional
DNA nanostructure consists of a disk connected to an external ring in two,
diametrically opposite points. A single stranded DNA, named probe, was connected
to two edges of the disk perpendicularly to the axis of constrain. In the
presence of a hybridizing target molecule, the probe coiled into a double helix
that stretched the inner disk forcing the edges to move toward each other. The
addition of a third single stranded molecule that displaced the target from the
probe restored the initial state of the origami. Operation, dimension and shape
were carefully characterized by combining microscopy and fluorescence techniques.
PMID- 22047683
TI - Long-term (<= 50 years) results of patients after mitral valve commissurotomy--a
single-center experience.
AB - OBJECTIVE: Currently, in Middle Europe, closed and open mitral valve
commissurotomy (MVC) is rarely done and has been replaced by catheter-based
balloon procedures. Especially under these circumstances, data on the long-term
outcomes after surgical interventions are important. METHODS: From 1955 to 1989,
268 patients (75 male and 193 female patients) with mostly rheumatic or
infectious mitral stenoses underwent closed (n = 151) or open (n = 117) surgical
procedures. The mean age at surgery was 41.2 +/- 11.1 years; 19 patients (7.1%)
died within the first 30 days after surgery. RESULTS: The 50-year follow-up was
complete for 215 patients (80.2%). The survival rate at 10, 20, and 30 years
after surgery was 80.2%, 58.6%, and 41.8%, respectively. The differences after
closed and open MVC were nonsignificant. At the latest follow-up, 32 patients
were alive and had a mean New York Heart Association functional classification of
2.7. The 10-, 20-, and 30-year freedom from reoperation rate was 93.2%, 82.9%,
and 76.0% for the closed intervention group and 88.5%, 80.3%, and 78.7% for the
open intervention groups. Again, the differences were nonsignificant. The main
cause for reoperation was recurrent fibrosis of the mitral valve. Most patients
(n = 51) received mechanical valves, 5 a bioprothesis, and 8 repeat MVC. Four
patients required a third intervention. CONCLUSIONS: In Middle Europe, closed and
open MVCs are now rarely performed, but the ultra-long-term results are excellent
and serve as a standard for the now-established balloon valvuloplasty. MVCs
remain an option for pregnant women. In third world clinical conditions, closed
MVC remains a less expensive alternative.
PMID- 22047684
TI - Effects of glutaraldehyde concentration, pretreatment time, and type of tissue
(porcine versus bovine) on postimplantation calcification.
AB - OBJECTIVE: Our objective was to evaluate the effects of glutaraldehyde (GA)
concentration, time of pretreatment, and type of tissue (porcine vs bovine) on
quantitative and qualitative postimplant calcification of tissues. METHODS:
Freshly obtained porcine and bovine pericardial tissues were each treated with
increasing concentrations of GA (controls, 0.3125%, 0.625%, and 1.2%) for a fixed
time (15 minutes) or increasing exposure times (5, 10, 20, and 30 minutes) at a
fixed concentration of GA (0.625%). Pretreated tissues were subcutaneously
implanted in 10-week-old Sprague-Dawley rats for 45 days before explantation.
Quantitative calcium analysis was performed by flame atomic spectrophotometry.
Histologic examination of tissue samples with hematoxylin and eosin and von Kossa
staining was performed for cellular and inflammatory response, autolysis, and
calcification. RESULTS: Two-way analysis of variance indicated significantly
greater calcium levels at 1.2% compared with each lower concentration for both
porcine and bovine samples (P < .01). Significantly lower calcium levels were
detected with increased exposure time in porcine samples (F = 6.97; P < .001);
however, no significant differences in calcium levels were observed between
different exposure times for bovine samples (F = 1.46; P = .23). Histologic
evidence of inflammatory response with infiltration with mononuclear cells,
fibroblasts, and histiocytes was seen in all grafts; however, it varied from mild
to severe without any pattern. There were no differences in degree or pattern of
inflammatory response according to GA concentration or time of exposure.
Estimation of amount of calcification by histologic examination correlated with
the quantitative assay. CONCLUSIONS: Increasing GA concentration leads to greater
calcification with a sharp rise in calcium levels above a concentration of
0.625%, in both bovine and porcine pericardial tissues. At a concentration of
0.625%, increasing pretreatment time is inversely related to tissue calcification
for porcine pericardium but not for bovine pericardium. Differences in the tissue
composition in terms of cellular content and composition of the extracellular
matrix could account for the observed findings.
PMID- 22047685
TI - Bioengineered self-seeding heart valves.
AB - OBJECTIVE: Mechanical and biological prostheses are used to replace damaged heart
valves but are associated with significant morbidities. Although there is
increased interest in bioengineering cell-seeded heart valve scaffolds, it is a
time-consuming and technically difficult process. The goal of this project was to
engineer self-seeding heart valves that mature quickly in vivo and have a shorter
preparation time. METHODS: Porcine pulmonary valves were decellularized using
detergent methods and then either (1) left untreated (unconjugated, n = 6), (2)
reseeded with autologous endothelial progenitor cell-derived endothelial cells
(cell-seeded, n = 4), or (3) conjugated with CD133 antibodies (conjugated, n =
8). The valve constructs were transplanted into the pulmonary position of sheep
using standard surgical techniques. After 1 or 3 months, the implants were
removed and assessed for cell and matrix content as well as biomechanical
properties. RESULTS: Endothelial cells expressing von Willebrand factor lined the
entire length of both ventricular and arterial surfaces of conjugated valves by 1
month after implantation. Interstitial cell and structural protein content of
conjugated valves increased from 1 month to 3 months with interstitial expression
of metalloproteinase-9 and new collagen formation. In contrast, there were few
endothelial or interstitial cells associated with unconjugated, or cell-seeded
valves at any time point. No calcification or thrombi were noted on any of the
valves. Young's modulus and tensile strength was greater in the conjugated valves
versus unconjugated or cell-seeded valves. CONCLUSIONS: Results indicate that
tissue-engineered heart valve replacement constructs can be made quickly and
therefore may be a clinically relevant option for patients needing heart valve
surgery in a timely fashion.
PMID- 22047686
TI - Quality of life of patients after retropubic prostatectomy - pre- and
postoperative scores of the EORTC QLQ-C30 and QLQ-PR25.
AB - BACKGROUND: Patients with newly diagnosed early stage prostate cancer (PCa) face
a difficult choice of different treatment options with curative intention. They
must consider both goals of optimising quantity and quality of life. The quality
of life (QoL) is a psychometric outcome which is measured using validated
questionnaires. Only few data are published concerning pre - and postoperative
QoL. METHODS: This study investigated pre perative QoL of 185 patients who
consecutively underwent open radical retropubic prostatectomy for organ-confined
PCa to postoperative QoL of another 185 patients. The EORTC QLQ-C30, EORTC
QLQPR25 module and 24 h ICS pad test were used (mean follow-up 28.6 months).
RESULTS: The examined symptom scores of the EORTC QLQ-PR25 were on lowest level.
In the dyspnoea symptom score differences of age emerged: the amount of patients
who are short of breath rose significantly in older patients after surgery (p <
0.05 paired, two-tailed student's t-test).. Lastly, the urinary symptom score was
found postal-therapeutically low; this fact was age independent. The results of
sexual symptom score need to be taken into consideration, since prostatectomy
resulted in a significant reduction of sexual activity independent of age. All
functioning scales postoperatively reached high values without significant
changes (p > 0.05 student's t-test ), which implies a high QoL after surgery. A
reliable and satisfying status of continence was found in our patients after
retropubic prostatectomy. A high rate of patients (89.2%) would choose retropubic
prostatectomy again. CONCLUSION: Retropubic prostatectomy represents a reliable
and accepted procedure in the treatment of organ-confined PCa. For the first time
it could be shown that patients' QoL remained on a high level after retropubic
prostatectomy. Nevertheless, the primary avoidance or postoperative therapy of
erectile dysfunction should be in the focus of surgeons.
PMID- 22047687
TI - Synthesis and evaluation of a bifunctional chelate for development of Bi(III)
labeled radioimmunoconjugates.
AB - A new bifunctional ligand C-DEPA was designed and synthesized as a component for
antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer. C-DEPA
was conjugated to a tumor targeting antibody, trastuzumab, and the corresponding
C-DEPA-trastuzumab conjugate was evaluated for radiolabeling kinetics with
(205/6)Bi. C-DEPA-trastuzumab conjugate rapidly bound (205/6)Bi, and (205/6)Bi-C
DEPA-trastuzumab conjugate was stable in human serum for 72 h. The in vitro
radiolabeling kinetics and serum stability data suggest that C-DEPA is a
potential chelate for preclinical RIT applications using (212)Bi and (213)Bi.
PMID- 22047688
TI - CCR2 receptor antagonists: optimization of biaryl sulfonamides to increase
activity in whole blood.
AB - A series of biarylsulfonamides was identified as hCCR2 receptor antagonist but
suffered from high plasma protein binding resulting in a >100 fold shift in
activity in a functional GTPgammaS assay run in tandem in the presence and
absence of human serum albumin. Introduction of an aryl amide with
ethylenediamine linker led to compounds with reduced shifts and improved activity
in whole blood.
PMID- 22047689
TI - Novel amino-piperidines as potent antibacterials targeting bacterial type IIA
topoisomerases.
AB - We have identified a series of amino-piperidine antibacterials with a good broad
spectrum potency. We report the investigation of various subunits in this series
and advanced studies on compound 8. Compound 8 possesses good pharmacokinetics,
broad spectrum antibacterial activity and demonstrates oral efficacy in a rat
lung infection model.
PMID- 22047690
TI - Conjugation of spermine enhances cellular uptake of the stapled peptide-based
inhibitors of p53-Mdm2 interaction.
AB - We report the first synthesis of the C-terminally spermine-conjugated stapled
peptide-based inhibitors of the p53-Mdm2 interaction. Subsequent biological,
biophysical and cellular uptake assays with the spermine-conjugated stapled
peptides revealed that spermine conjugation minimally affects biological activity
while significantly increases peptide helicity and cellular uptake without
apparent cytotoxicity.
PMID- 22047691
TI - The discovery of AZD9164, a novel muscarinic M3 antagonist.
AB - The optimization of a new series of muscarinic M(3) antagonists is described,
leading to the identification of AZD9164 which was progressed into the clinic for
evaluation of its potential as a treatment for COPD.
PMID- 22047692
TI - Nicotinic acids: liver-targeted SCD inhibitors with preclinical anti-diabetic
efficacy.
AB - An in vitro screening protocol was used to transform a systemically-distributed
SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic
acid moiety enables molecular recognition by OATP transporters, as demonstrated
by uptake studies in transfected cell lines, and likely serves as a critical
component of the observed liver-targeted tissue distribution profile. Preclinical
anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver
targeting SCD inhibitor 10, and studies with a close-structural analog devoid of
SCD1 activity, suggest this efficacy is a result of on-target activity.
PMID- 22047693
TI - Antifungal activity of 2alpha,3beta-functionalized steroids stereoselectively
increases with the addition of oligosaccharides.
AB - Invasive fungal infections pose a significant problem to the immune-compromised.
Moreover, increased resistance to common antifungals requires development of
novel compounds that can be used to treat invasive fungal infections. Naturally
occurring steroidal glycosides have been shown to possess a range of functional
antimicrobial properties, but synthetic methodology for their development hinders
thorough exploration of this class of molecules and the structural components
required for broad spectrum antifungal activity. In this report, we outline a
novel approach to the synthesis of glycoside-linked functionalized 2alpha,3beta
cholestane and spirostane molecules and present data from in vitro screenings of
the antifungal activities against human fungal pathogens and as well as mammalian
cell toxicity of these derivatives.
PMID- 22047694
TI - Antiprotozoal activity of proton-pump inhibitors.
AB - Parasitic diseases are still a major health problem in developing countries. In
our effort to find new antiparasitic agents, in this Letter we report the in
vitro antiprotozoal activity of omeprazole, lansoprazole, rabeprazole and
pantoprazole against Trichomonas vaginalis, Giardia intestinalis and Entamoeba
histolytica. Molecular modeling studies were an important tool to highlight the
potential antiprotozoal activity of these drugs. Experimental evaluations
revealed a strong activity for all compounds tested. Rabeprazole and pantoprazole
were the most active compounds, having IC(50) values in the nanomolar range,
which were even better than metronidazole, the drug of choice for these
parasites.
PMID- 22047695
TI - Exploration of in vitro time point quantitative evaluation of newly synthesized
benzimidazole and benzothiazole derivatives as potential antibacterial agents.
AB - Present communication deals with the in vitro time point quantitative
antibacterial evaluation of newly synthesized 1,2-disubstituted benzimidazoles
(3a-p) and 2-substituted benzothiazoles (5a-h) against Gram-positive bacteria
Staphylococcus aureus, Bacillus cereus, and Gram-negative bacteria Vibrio
cholerae, Shigella dysenteriae and Escherichia coli. These compounds were
synthesized under mild reaction conditions using Al(2)O(3)-Fe(2)O(3) nanocrystals
as heterogeneous catalyst. Bio-evaluation studies revealed that, compounds 3a, 5a
and 5d exhibited moderate to good antibacterial activity against all the tested
bacterial stains. The compounds 3a, 3f and 5a have shown enhanced inhibitory
activity compared with standard antibacterial drug ciprofloxacin against V.
cholerae, B. cereus, and S. dysenteriae, respectively. Additionally, the
compounds 3a, 3e, 3f, 3h and 5b displayed complete bactericidal activity within
24 h, whereas ciprofloxacin took 48 h to kill those bacteria completely.
PMID- 22047696
TI - Structure-activity relationships of ganoderma acids from Ganoderma lucidum as
aldose reductase inhibitors.
AB - A series of lanostane-type triterpenoids, known as ganoderma acids were isolated
from the fruiting body of Ganoderma lucidum. Some of these compounds were
identified as active inhibitors of the in vitro human recombinant aldose
reductase. To clarify the structural requirement for inhibition, some structure
activity relationships were determined. Our structure-activity studies of
ganoderma acids revealed that the OH substituent at C-11 is an important feature
and the carboxylic group in the side chain is essential for the recognition of
aldose reductase inhibitory activity. Moreover, double bond moiety at C-20 and C
22 in the side chain contributes to improving aldose reductase inhibitory
activity. In the case of ganoderic acid C2, all of OH substituent at C-3, C-7 and
C-15 is important for potent aldose reductase inhibition. These results provide
an approach to understanding the structural requirements of ganoderma acids from
G. lucidum for aldose reductase inhibitor. This understanding is necessary to
design a new-type of aldose reductase inhibitor.
PMID- 22047697
TI - Fluorescent reporters of monoamine transporter distribution and function.
AB - Serotonin is a monoamine serving as a chemical messenger in diverse brain
regions, as well as in blood and various other organs. We synthesized six
ethylamine functionalized fluorophores as fluorescent probes for serotonin. The
one with best spectral properties and aqueous solubility, 6-amino-2-(2
aminoethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, was studied in detail both in
vivo and in vitro. It was shown to act as a ligand for serotonin transporter
(SERT) without acute cerebral or cardiovascular toxicity or adverse effects.
Fluorescent serotonin analogs can be used for direct visualization of SERT
distribution and activity in live tissue.
PMID- 22047698
TI - Novel cytotoxic chalcones from Litsea rubescens and Litsea pedunculata.
AB - Two novel flavonoids with chalcone skeleton, together with seven known
flavonoids, were isolated from the stem barks of Litsea rubescens and Litsea
pedunculata. The structures of the new compounds were elucidated on the basis of
spectral methods including IR, UV, 1D and 2D NMR. The new chalcones were found to
contain the rare epoxy or ethylidenedioxy group. This is the first report on the
presence of chalcone in the plant genus Litsea. The cytotoxic potential of two
new chalcones was evaluated in vitro against three human tumor cell lines. Both
new chalcones displayed potent cytotoxic activities against myeloid leukaemia (HL
60) and epidermoid carcinoma (A431) cell lines and more active than cisplatin
(DDP). Interestingly, compound 1 exhibited cytotoxic activity against HL-60 with
IC(50) value 2.1-fold more sensitive to DDP.
PMID- 22047699
TI - Use of self-expandable stents in the treatment of bariatric surgery leaks: a
systematic review and meta-analysis.
AB - BACKGROUND: Bariatric surgery leaks can result in significant morbidity and
mortality. Endoscopic placement of self-expandable stents (SESs) is emerging as a
less-invasive alternative to surgery for the treatment of leaks. OBJECTIVE: To
evaluate the success of SESs in the treatment of bariatric surgery leaks. DESIGN:
Studies using SESs in the management of bariatric surgery leaks were selected.
Success of SES treatment was defined as radiographic evidence of leak closure
after stent removal. Articles were searched in MEDLINE, PubMed, Ovid, and
Cochrane Register of Controlled Trials. Pooled proportions were calculated by
using fixed- and random-effects models. Publication bias was calculated by using
the Begg-Mazumdar and Harbord bias estimators. RESULTS: A total of 189 relevant
articles were reviewed of which 7 studies (67 patients with leaks) met inclusion
criteria. The pooled proportion of successful leak closures by using SESs was
87.77% (95% CI, 79.39%-94.19%). The pooled proportion of successful endoscopic
stent removal was 91.57% (95% CI, 84.22%-96.77%). Stent migration was noted in
16.94% (95% CI, 9.32%-26.27%). Test of heterogeneity gave a P value >.10. There
was no publication bias. LIMITATIONS: Small retrospective studies, different
types of stents used. CONCLUSION: Endoscopic placement of SESs is a minimally
invasive, safe, and effective alternative in the management of leaks after
bariatric surgery. The use of SESs can minimize the need for surgical revision
and improve patient outcomes.
PMID- 22047700
TI - Single-operator cholangioscopy for the extraction of cystic duct stones (with
video).
PMID- 22047701
TI - The effect of hand dominance on martial arts strikes.
AB - The main goal of this study was to compare dominant and non-dominant martial arts
palm strikes under different circumstances that usually happen during martial
arts and combative sports applications. Seven highly experienced (10+/-5 years)
right hand dominant Kung Fu practitioners performed strikes with both hands,
stances with left or right lead legs, and with the possibility or not of stepping
towards the target (moving stance). Peak force was greater for the dominant hand
strikes (1593.76+/-703.45 N vs. 1042.28+/-374.16 N; p<.001), whereas no
difference was found in accuracy between the hands (p=.141). Additionally, peak
force was greater for the strikes with moving stance (1448.75+/-686.01 N vs.
1201.80+/-547.98 N; p=.002) and left lead leg stance (1378.06+/-705.48 N vs.
1269.96+/-547.08 N). Furthermore, the difference in peak force between strikes
with moving and stationary stances was statistically significant only for the
strikes performed with a left lead leg stance (p=.007). Hand speed was higher for
the dominant hand strikes (5.82+/-1.08 m/s vs. 5.24+/-0.78 m/s; p=.001) and for
the strikes with moving stance (5.79+/-1.01 m/s vs. 5.29+/-0.90 m/s; p<.001). The
difference in hand speed between right and left hand strikes was only significant
for strikes with moving stance. In summary, our results suggest that the stronger
palm strike for a right-handed practitioner is a right hand strike on a left lead
leg stance moving towards the target.
PMID- 22047702
TI - Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other
carbapenems? A review of the evidence.
AB - The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have
been a mainstay of treatment for patients with serious hospital infections caused
by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram
negative pathogens as well as mixed aerobic/anaerobic infections. When ertapenem,
a group 1 carbapenem, was introduced, questions were raised about the potential
for ertapenem to select for imipenem- and meropenem-resistant Pseudomonas.
Results from ten clinical studies evaluating the effect of ertapenem use on the
susceptibility of Pseudomonas to carbapenems have uniformly shown that ertapenem
use does not result in decreased Pseudomonas susceptibility to these
antipseudomonal carbapenems. Here we review these studies evaluating the evidence
of how ertapenem use affects P. aeruginosa as well as provide considerations for
ertapenem use in the context of institutional stewardship initiatives.
PMID- 22047703
TI - Retrospective case-control analysis of patients with staphylococcal infections
receiving daptomycin or glycopeptide therapy.
AB - Glycopeptides have been considered the antimicrobials of choice for serious
meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant
coagulase-negative staphylococci (MR-CoNS) infections for several years.
Daptomycin is a new option for the treatment of these infections, including those
exhibiting reduced susceptibility to glycopeptides. The aim of this study was to
compare glycopeptides and daptomycin for the treatment of infections caused by
MRSA or MR-CoNS. Data for 106 patients with bloodstream infections (bacteraemia
or infective endocarditis) or skin and soft-tissue infections (SSTIs) were
retrospectively reviewed, of which 43 were treated with daptomycin (DAP group)
and 63 were treated with vancomycin or teicoplanin (GLYCO group). Patients
included in the two comparison groups were homogeneous in terms of age, risk
factors and clinical severity. Aetiology was mainly represented by MRSA in both
groups, followed by various species of MR-CoNS. Daptomycin was used more
frequently in patients with central venous catheter-associated bacteraemia or
pacemaker-associated infection. Patients with SSTIs included in the GLYCO group
had a longer mean duration of antibiotic therapy (18.2 days vs. 14.6 days;
P=0.009) and a longer mean length of hospital stay (28.2 days vs. 19.6 days;
P=0.01) compared with those included in the DAP group. A longer mean duration of
antibiotic therapy was also observed in patients with bloodstream infections
receiving glycopeptide therapy (25.6 days vs. 18 days; P=0.004). In conclusion,
the good clinical efficacy of daptomycin is associated with a more rapid
resolution of the clinical syndrome and a reduced length of hospitalisation. This
latter aspect may have important pharmacoeconomic implications, promoting the use
of daptomycin in the clinical setting.
PMID- 22047704
TI - Co-infection with Opisthorchis viverrini and Haplorchis taichui detected by human
fecal examination in Chomtong district, Chiang Mai Province, Thailand.
AB - Diseases caused by the liver fluke, Opisthorchis viverrini and the minute
intestinal fluke, Haplorchis taichui, are clinically important, especially in the
Northeast and North regions of Thailand. It is often difficult to distinguish
between these trematode species using morphological methods due to the similarity
of their eggs and larval stages both in mixed and co-infections. A sensitive,
accurate, and specific detection method of these flukes is required for an
effective epidemiological control program. This study aimed to determine the
prevalence of O. viverrini and H. taichui infections in human feces by using
formalin-ether sedimentation and high annealing temperature random amplified
polymorphic DNA (HAT-RAPD) PCR methods. Fecal specimens of people living along
the Mae Ping River, Chomtong district were examined seasonally for trematode eggs
using a compound microscope. Positive cases were analyzed in HAT-RAPD, DNA
profiles were compared with adult stages to determine the actual species
infected, and specific DNA markers of each fluke were also screened. Our results
showed that out of 316 specimens, 62 were positive for fluke eggs which were pre
identified as O. viverrini and H. taichui. In addition, co-infection among these
two fluke species was observed from only two specimens. The prevalence of H.
taichui infections peaked in the hot-dry (19.62%), gradually decreased in the
rainy (18.18%), and cool-dry seasons (14.54%), respectively. O. viverrini was
found only in the hot-dry season (6.54%). For molecular studies, 5 arbitrary
primers (Operon Technologies, USA) were individually performed in HAT-RAPD-PCR
for the generation of polymorphic DNA profiles. The DNA profiles in all 62
positives cases were the same as those of the adult stage which confirmed our
identifications. This study demonstrates the mixed infection of O. viverrini and
H. taichui and confirms the extended distribution of O. viverrini in Northern
Thailand.
PMID- 22047705
TI - Evaluation of perseveration in relation to panic-relevant responding: an initial
test.
AB - BACKGROUND: Perseveration reflects the tendency to engage in a behavior even when
it is no longer rewarding nor produces the expected consequences. METHOD: The
current study explored whether (1) individuals endorsing a recent (past 2 years)
history of nonclinical panic attacks would report greater levels of perseveration
compared to individuals without such a history; (2) whether individuals endorsing
higher levels of perseveration would evidence greater panic-relevant responding
to a 4-minute 10% carbon dioxide-enriched air challenge. RESULTS: Results
indicated that individuals with, compared to without, a positive panic attack
history endorsed significantly greater levels of perseveration. Additionally,
greater pre-challenge levels of perseveration significantly predicted greater
panic attack symptom severity as well as self-reported anxiety; these significant
effects were evident above and beyond the variance accounted for by sex, trait
level negative affectivity, panic attack status, and distress tolerance as well
as shared variance with the related constructs of persistence and perfectionism.
DISCUSSION: Together, the current findings provide initial, albeit preliminary,
support for the utility of investigating perseveration in relation to models of
panic psychopathology specifically, and offer a further empirical context for
perseveration-psychopathology relations in general.
PMID- 22047706
TI - The utility of fluorescence in situ hybridization analysis in diagnosing
myelodysplastic syndromes is limited to cases with karyotype failure.
AB - Fluorescence in situ hybridization (FISH) is being used increasingly in
cytogenetic diagnosis of myelodysplastic syndromes (MDS). However, the utility of
FISH in this role has not been well-defined. A total of 249 de novo MDS patients
were submitted to karyotyping and FISH analysis for -5/del(5)(q31),
7/del(7)(q31), +8, -17/i(17)(q10), del(20)(q12), and -Y. Of the 234 patients with
available karyotypic data, 143 cases (60.9%) demonstrated normal karyotype and 91
cases (39.1%) showed abnormal karyotype. FISH confirmed R-banding findings in
96.6% (226/234) of samples with successful karyotyping and detected cytogenetic
abnormalities in 46.7% (7/15) of cases with karyotype failure. Of the 3.4%
(8/234) patients showing discrepancies between FISH and R-banding, FISH revealed
cytogenetic abnormalities in four patients with normal karyotypes and four
patients with complex karyotypes. These results highlight FISH analysis has
limited value in MDS cases with successful karyotyping and is only informative in
MDS cases with karyotype failure.
PMID- 22047707
TI - Tyrosine kinase inhibitor therapy for acute myeloid leukemia with late-appearing
Philadelphia chromosome.
PMID- 22047708
TI - Vitamin D insufficiency predicts time to first treatment (TFT) in early chronic
lymphocytic leukemia (CLL).
AB - Although vitamin D insufficiency is related to inferior prognosis in some
cancers, limited data exist in hematologic malignancies. We evaluated the
relationship between 25(OH)D serum levels and time to first treatment (TFT), a
disease-specific end point, in 130 previously untreated Binet stage A chronic
lymphocytic leukemia (CLL) patients. Measurement of 25(OH)D was performed by
means of a direct, competitive chemiluminescence immunoassay using the DiaSorin
LIAISON 25(OH)D TOTAL assay (DiaSorin, Inc., Stillwater, Minnesota). Overall, 41
patients (31.5%) had severe vitamin D insufficiency (<10 ng/mL), 66 (50.7%) had
mild to moderate insufficiency (10-24 ng/mL), and 23 (17.6%) had 25(OH)D levels
within the optimal range (25-80 ng/mL), with no relationship with between the
season of sample collection and 25(OH)D level (P=0.188). A patient stratification
according to these 3 groups led to significant difference in terms of TFT, with
vitamin D insufficient patients having the shortest TFT (P=0.02). With respect to
continuous 25(OH)D levels and clinical outcome, TFT was shorter as 25(OH)D
decreased until a value of 13.5 ng/mL at which point the association of 25(OH)D
and TFT remained constant. As a matter of fact, the 25(OH)D value of 13.5 ng/mL
identified two patients subsets with different TFT risk (HR=1.91; 95% CI=1.06
3.44; P=0.03). In multivariate analysis the variable entering the model at a
significant level were mutational status of IgVH (P<0.0001), serum thymidine
kinase (P=0.02) and absolute lymphocyte count (P=0.03). Thus confirming the Mayo
clinic experience, our data provide further evidence that 25(OH)D levels may be
an important host factor influencing TFT of Binet stage A patients. Whether
normalizing vitamin D levels may delay disease-progression of patients with early
disease will require testing in future trials.
PMID- 22047709
TI - DNA repair gene XPD and XRCC1 polymorphisms and the risk of febrile neutropenia
and mucositis in children with leukemia and lymphoma.
AB - The aim of the study is to investigate association between DNA repair gene XPD
and XRCC1 polymorphisms and febrile neutropenia (FN) and mucositis. The study
population consisted of 29 children with Burkitt lymphoma and 61 children with
acute lymphoblastic leukemia. Analysis revealed that XRCC1194Trp allele showed a
protective effect against longer FN and mucositis. There was also statistically
increased risk for severe mucositis in patients with XRCC1Arg399Gln polymorphism.
There are no studies that have examined this relationship before. Further studies
with larger cohorts are needed to clarify the association.
PMID- 22047710
TI - piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor
suppressive activity in human gastric cancer cells.
AB - Piwi-interacting RNAs (piRNAs), new non-coding small RNAs, are association with
chromatin organization, messenger RNA stability and genome structure. However,
the roles of piRNA in carcinogenesis are not clearly defined. By using real-time
reverse transcription-polymerase chain reaction technology, we found that the
expression level of piR-823 in gastric cancer tissues was significant lower than
that in non-cancerous tissues. After increase the level of piR-823 in gastric
cancer cells, cell growth was inhibited. The results of xenograft nude mice model
confirmed its tumor suppressive properties. All of the evidences indicated that
piR-823 play a crucial role in the occult of gastric cancer.
PMID- 22047711
TI - Protective and therapeutic effects of licorice in rats with acute tubular
necrosis.
AB - OBJECTIVES: Various protective and therapeutic effects such as antioxidant, anti
inflammatory, anticancer, antihistaminic, and antibacterial effects have been
depicted for licorice. However, its biological effects in the kidney are still
not clear. Therefore, we aimed to investigate the efficiency of licorice in rats
with gentamicin (GM)-induced acute tubular necrosis. DESIGN AND METHODS: Rats
were randomized into the control group (only saline for 12 days), licorice group
(licorice for 12 days), GM group (GM for 12 days), GM + licorice group, and
licorice-treated GM group (licorice for 12 days after taking GM for 12 days).
Blood urea, creatinine, and uric acid levels were measured and histopathological
analyses of the kidneys were performed. The oxidative side of oxidant-antioxidant
balance was evaluated by detecting lipid peroxidation (LPO) and total peroxide
levels, and antioxidative side was determined by measuring total antioxidant
capacity (TAC) and reduced glutathione (GSH) levels in plasma and kidney tissues.
RESULTS: The oxidant-antioxidant balance seemed to be shifted to the oxidative
side in the GM group when compared with the control and GM + licorice groups. In
GM group, biochemical profiles showed a remarkable increase in blood uric acid,
urea, and creatinine levels, and depletion of renal tissue and plasma TAC and GSH
levels. In addition, histopathologic studies revealed severe acute tubular
necrosis, congestion, and hyaline casts, verifying GM-induced nephrotoxicity.
Licorice was effective in reduction of blood urea, creatinine, and uric acid
levels, and also effective in decreasing the tubular necrosis score. Licorice
treatment also significantly reduced LPO and total peroxide levels, and increased
TAC and GSH levels in both renal tissue and blood. Moreover, these changes in
rats subjected to the combined therapy (GM + licorice) were significantly less
than those of GM group. CONCLUSIONS: Licorice ameliorates GM-induced
nephrotoxicity and oxidative damage by scavenging oxygen free radicals,
decreasing LPO, and improving antioxidant defense.
PMID- 22047712
TI - [Sociodemographic factors and satisfaction related to the care received by women
with breast cancer. Multicentre study].
AB - OBJECTIVES: Evaluate the level of satisfaction in the Medical Oncology Services
in our Community of women with breast cancer, and analyse the influence of
sociodemographic and clinical factors on their satisfaction. MATERIAL AND
METHODS: Cross-sectional multicentre study using an anonymous and voluntary
questionnaire completed by 225 women diagnosed with breast cancer. The tool used
was the modified SERVQHOS, adapted to our context. We collected demographic and
clinical data. To determine the reliability of the tool after the adjustments, a
Cronbach's alpha analysis was performed. A descriptive analysis was also
performed, as well as non-parametric statistics to study the influence of
demographic variables on satisfaction. RESULTS: The best evaluated aspects were
the kindness of the staff [4.30+/-0.83 (2-5)], the confidence transmitted by them
[4.23+/-0.79 (2-5)] and personal treatment [4.12+/-0.88 (2-5)]. The worst
evaluated was the ease of getting to the hospital [3.06+/-0.99 (1-5)], waiting
time [3.16+/-1.00 (1-5)], state of consultations rooms [3.38+/-0.99 (1-5)] and
punctuality of the sessions [3.38+/-1.05 (1-5)]. The overall satisfaction was
4.04+/-0.82 (1-5). Age influenced their assessment of the personal appearance of
the staff (P=.04), the state of consultations rooms (P<00), the ease of getting
to the hospital, and the quantity and quality of information received (P=01).
Educational level influenced their satisfaction with personal appearance of the
staff (P =03) and the state of consultations rooms (P=03). Women who worked and
those who were temporary disabled women evaluated the appearance of personnel
worst (P=02). The time from the diagnosis affected the satisfaction with the
staff willingness to help (P<00) and therapy attendance, and the satisfaction
with the ability to understand their needs (P=03). CONCLUSIONS: The individual
characteristics of the participants influence their satisfaction. We have been
able to identify deficient areas from their point of view, identifying important
improvement opportunities in several aspects of care to work on in order to
increase the quality of care.
PMID- 22047713
TI - Demonstration of genes encoding virulence and virulence life-style factors in
Brachyspira spp. isolates from pigs.
AB - The distribution of many genes encoding virulence and virulence life-style (VL-S)
factors in Brachyspira (B.) hyodysenteriae and other Brachyspira species are
largely unknown. Their knowledge is essential e.g. for the improvement of
diagnostic methods targeting the detection and differentiation of the species.
Thus 121 German Brachyspira field isolates from diarrhoeic pigs were
characterized down to the species level by restriction fragment length
polymorphism analysis of the nox gene and subsequently subjected to polymerase
chain reaction detecting VL-S genes for inner (clpX) and outer membrane proteins
(OMPs: bhlp16, bhlp17.6, bhlp29.7, bhmp39f, bhmp39h), hemolysins (hlyA/ACP,
tlyA), iron metabolism (ftnA, bitC), and aerotolerance (nox). For comparison, B.
hyodysenteriae reference strains from the USA (n=7) and Australia (2) were used.
Of all genes tested only nox was detected in all isolates. The simultaneous
presence of both the tlyA and hlyA/ACP was restricted to the species B.
hyodysenteriae. The hlyA infrequently occurred also in weakly hemolytic
Brachyspira. Similarly to tlyA and hlyA all B. hyodysenteriae strains contained
the ferritin gene ftnA which was also found in two Brachyspira intermedia
isolates. OMP encoding genes were present in B. hyodysenteriae field isolates in
rates of 0% (bhlp17.6, bhmp39h), 58.1% (bhlp29.7), and 97.3% (bhmp39f). Since the
study revealed a high genetic heterogeneity among German B. hyodysenteriae field
isolates differentiating them from USA as well as Australian strains, targets for
diagnostic PCR were limited to the nox gene (genus specific PCR) as well as to
the species specific nox(hyo) gene and the combination of hlyA and tlyA which
allow to specifically detect B. hyodysenteriae.
PMID- 22047714
TI - The surface-localised alpha-enolase of Mycoplasma suis is an adhesion protein.
AB - Mycoplasma suis belongs to the haemotrophic mycoplasmas which colonise red blood
cells of a wide range of vertebrates. Adhesion to red blood cells is the crucial
step in the unique lifecycle of M. suis. Due to the lack of a cultivation system,
identification of adhesion structures has been difficult. So far, only one
adhesion protein, i.e. MSG1 was identified. In order to determine further
adhesion molecules of M. suis, we screened genomic M. suis libraries and
performed Southern blot hybridisation analyses of genomic M. suis DNA. The alpha
enolase of M. suis was identified and analysed genetically and functionally. The
encoding gene has 1623 bp in size. The deduced amino acid sequence showed an
overall identity of 59.6-65.1% to alpha-enolases of other pathogenic mycoplasmas.
The 540 aa M. suis alpha-enolase displays a size extension of about 90 aa in
comparison to alpha-enolases of other mycoplasmas. Recombinant alpha-enolase
expressed in Escherichia coli demonstrated immunogenicity in experimentally
infected pigs. Immunoblot, confocal laser scanning microscopy and immune electron
microscopy analysis using antibodies against recombinant alpha-enolase, indicate
the membrane and surface localisation of native alpha-enolase in M. suis, though
no typical signal sequences exist. Furthermore, we showed that recombinant alpha
enolase binds to porcine erythrocyte lysate in a dose-dependent manner. E. coli
transformants which express alpha-enolase on their surface acquire the ability to
adhere to porcine red blood cells. In conclusion, our observations indicate that
alpha-enolase could be involved in the adhesion of M. suis to porcine red blood
cells.
PMID- 22047715
TI - In vitro culture of blastocystis hominis in three liquid media and its usefulness
in the diagnosis of blastocystosis.
AB - BACKGROUND: Blastocystis hominis is a common protozoan in the human intestinal
tract and can cause the so-called blastocystosis characterized by diarrhea. To
date, its identification has depended on the discovery of vacuolar, granular,
amoebic, or cystic forms in stool samples using wet mount smears, iodine
staining, trichrome staining, or iron hematoxylin staining. The permanent
staining methods provide more positive findings. However, mercuric chloride
(HgCl(2))-based polyvinyl alcohol (PVA) and Schaudinn fixative are potentially
toxic and dangerous to laboratory personnel and, as hazardous chemicals, present
problems with disposal. METHODS: To determine whether in vitro culture could be
an environmentally safe alternative, the culture growth of B. hominis in three
commercially available liquid media (RPMI 1640, 199 Medium, and Dulbecco's
modified Eagle's medium (DMEM)) were observed and compared. The sensitivity and
specificity of these culture methods to identify B. hominis were compared with
those of existing methods used clinically. RESULTS: Conditions for the anaerobic
culture of B. hominis in these media were determined as follows: total inoculum
sizes no less than 10(5) cells; pH values ranging from 7.0 to 7.5; concentrations
of calf or horse serum ranging from 10% to 30% (vol/vol); basic antibiotics
added; peaking times at days 3, 6, and 9 (pH 7.5) or days 4 and 8 (or 9) (pH 7.0)
at 37 degrees C. No significant differences were noted in multiplication or
generation times for the cultivation of B. hominis (p>0.05). In 56 of 398
positive cases, the short-term in vitro culture method achieved the best
performance with regard to sensitivity and specificity of the five studied
methods. CONCLUSIONS: With the advantages of environmental safety, convenience in
preparation and storage, facility in morphologic discrimination, and outstanding
performance in terms of sensitivity and specificity, the in vitro culture method
could be applied to identify B. hominis for both clinical diagnosis and field
study purposes.
PMID- 22047716
TI - Nonrigid registration of CLSM images of physical sections with discontinuous
deformations.
AB - When biological specimens are cut into physical sections for three-dimensional
(3D) imaging by confocal laser scanning microscopy, the slices may get distorted
or ruptured. For subsequent 3D reconstruction, images from different physical
sections need to be spatially aligned by optimization of a function composed of a
data fidelity term evaluating similarity between the reference and target images,
and a regularization term enforcing transformation smoothness. A regularization
term evaluating the total variation (TV), which enables the registration
algorithm to account for discontinuities in slice deformation (ruptures), while
enforcing smoothness on continuously deformed regions, was proposed previously.
The function with TV regularization was optimized using a graph-cut (GC) based
iterative solution. However, GC may generate visible registration artifacts,
which impair the 3D reconstruction. We present an alternative, multilabel TV
optimization algorithm, which in the examined samples prevents the artifacts
produced by GC. The algorithm is slower than GC but can be sped up several times
when implemented in a multiprocessor computing environment. For image pairs with
uneven brightness distribution, we introduce a reformulation of the TV-based
registration, in which intensity-based data terms are replaced by comparison of
salient features in the reference and target images quantified by local image
entropies.
PMID- 22047717
TI - 2D-Qsar for 450 types of amino acid induction peptides with a novel substructure
pair descriptor having wider scope.
AB - BACKGROUND: Quantitative structure-activity relationships (QSAR) analysis of
peptides is helpful for designing various types of drugs such as kinase inhibitor
or antigen. Capturing various properties of peptides is essential for analyzing
two-dimensional QSAR. A descriptor of peptides is an important element for
capturing properties. The atom pair holographic (APH) code is designed for the
description of peptides and it represents peptides as the combination of thirty
six types of key atoms and their intermediate binding between two key atoms.
RESULTS: The substructure pair descriptor (SPAD) represents peptides as the
combination of forty-nine types of key substructures and the sequence of amino
acid residues between two substructures. The size of the key substructures is
larger and the length of the sequence is longer than traditional descriptors.
Similarity searches on C5a inhibitor data set and kinase inhibitor data set
showed that order of inhibitors become three times higher by representing
peptides with SPAD, respectively. Comparing scope of each descriptor shows that
SPAD captures different properties from APH. CONCLUSION: QSAR/QSPR for peptides
is helpful for designing various types of drugs such as kinase inhibitor and
antigen. SPAD is a novel and powerful descriptor for various types of peptides.
Accuracy of QSAR/QSPR becomes higher by describing peptides with SPAD.
PMID- 22047718
TI - Cumulative depression episodes predict later C-reactive protein levels: a
prospective analysis.
AB - BACKGROUND: Depression is associated with elevated levels of the inflammation
marker C-reactive protein (CRP); yet, the direction of this association remains
unclear. This study tested bi-directional longitudinal associations between CRP
and depression in a sample of adolescents and young adults. The study compared
the effect of current depression with the effect of cumulative episodes of
depression over time. METHODS: Nine waves of data from the prospective population
based Great Smoky Mountains Study (n = 1420) were used, covering children in the
community aged 9 to 16, 19, and 21 years old. Structured interviews were used to
assess depressive symptoms, depression diagnosis, and cumulative depressive
episodes. Bloodspots were collected at each observation and assayed for CRP
levels. RESULTS: CRP levels were not associated with later depression status. In
contrast, all depression-related variables displayed evidence of association with
later CRP levels. The associations with depressive symptoms and diagnostic status
were attenuated after controlling for covariates, particularly body mass index,
smoking, and medication use. The effect of cumulative depressive episodes,
however, continued to be significant after accounting for a range of covariates.
Body mass index, smoking behavior, and recent infections may mediate a portion of
the effect of cumulative episodes on later CRP, but cumulative depressive
episodes continued to predict CRP levels independently. CONCLUSIONS: The
occurrence of multiple depressive episodes exerted the greatest effect on later
CRP levels. This suggests that risk for the diseases of middle and old age-
cardiovascular and metabolic disease--may begin in childhood and depend, in part,
on long-term emotional functioning.
PMID- 22047720
TI - Ordered mesoporous carbon coating on cordierite: synthesis and application as an
efficient adsorbent.
AB - Ordered mesoporous carbon coating on the honeycomb cordierite substrate has been
prepared using low-polymerized phenolic resins as carbon sources and triblock
copolymer F127 as the structure directing agent via the evaporation induced self
assembly route. The high-resolution scanning electron microscopy (HRSEM),
transmission electron microscopy (TEM), and nitrogen sorption techniques prove
the hexagonally ordered pore arrays of carbon coating on the cordierite. The
honeycomb monolith adsorbents coated by ordered mesoporous carbons are directly
used without any activation, and exhibit adsorption capacities for chlorinated
organic pollutants in water with 200 mg/g for p-chlorophenol and 178 mg/g for p
chloroaniline (with respect to the net carbon coating), high adsorption ratio for
low-concentration pollutants, large processing volumes and reusability. More than
200 repeated times can be achieved without obvious loss in both adsorption
capacity and weight.
PMID- 22047719
TI - Frontal white matter integrity predictors of adult alcohol treatment outcome.
AB - BACKGROUND: Previous research has associated abnormalities in frontal lobe
functioning with alcohol relapse. In this study, we used diffusion tensor imaging
to investigate whether frontal white matter integrity measured at the start of
treatment differs between persons with alcohol use disorders (AUD) who sustain
treatment gains and those who return to heavy use after treatment. METHODS: Forty
five treatment-seeking AUD inpatients and 30 healthy control subjects were
included in the study. Six months after completing treatment, 16 of the AUD
participants had resumed heavy use (RHU) and 29 others remained abstinent or
drank minimally (treatment sustainers [TS]). Voxel-wise group comparisons (TS vs.
RHU) were performed on fractional anisotropy (FA), radial diffusivity (RD), and
axial diffusivity maps generated from each subject's diffusion tensor imaging
scan at the start of treatment. RESULTS: We found significantly lower FA and
significantly higher RD in the frontal lobes of the RHU group, relative to the TS
group. The RHU group data are consistent with previous reports of abnormal
frontal white matter tract abnormalities in persons with AUD. CONCLUSIONS: It is
possible that the lower FA and higher RD in the RHU group reflect microstructural
injury to frontal circuitries, and these may underlie the reduced cognitive
control amid heightened reward sensitivity associated with resumption of heavy
drinking.
PMID- 22047721
TI - Enhancing uranium solubilization in soils by citrate, EDTA, and EDDS chelating
amendments.
AB - A systematic study was made of the effects of three soil amendments on the
solubilization of uranium from a granitic soil. The aim was to optimize
solubilization so as to enhance bioavailability for the purposes of remediation.
The three amendments tested were with citrate, EDTA, and EDDS as chelating
agents. The effects of pH, chelator concentration, and leaching time were
studied. The most important factor in uranium solubilization was found to be the
pH. In the absence of chelating agents, the greatest solubilization was obtained
for alkaline conditions, with values representing about 15% of the total uranium
activity in the bulk soil. There were major differences in uranium solubilization
between the different amendments. The citrate treatment was the most efficient at
acidic pH, particularly with the greatest concentration of citrate tested (50
mmol kg(-1)) after 6 days of treatment. Under these conditions, the uranium
concentration in solution was greater by a factor of 356 than in the control
suspension, and represented some 63% of the uranium concentration in the bulk
soil. Under alkaline conditions, the EDTA and EDDS treatments gave the greatest
uranium activity concentrations in solution, but these concentrations were much
lower than those with the citrate amendment, and were not very different from the
control results. The uranium extraction yield with EDDS amendment was greater
than with EDTA.
PMID- 22047722
TI - Hydrous ferric oxide-resin nanocomposites of tunable structure for arsenite
removal: effect of the host pore structure.
AB - Hydrous ferric oxide (HFO) loaded hybrid sorbents are considered to be excellent
materials for arsenic removal from water. However, role of the host pore
structure in the performance of the composites is still unclear. In the current
study five HFO nanocomposites of similar HFO loadings (3.9-5.3% in Fe mass) were
fabricated for arsenite removal, using self-synthesized polystyrene (PS) resins
of similar particle sizes but different pore structures as hosts. Structure
analysis demonstrated that the particle size of HFO aggregates decreased with
decreasing pore size of PS. The adsorption of arsenite onto the nanocomposites
with PS of smaller average pore size achieved equilibrium faster. Analysis of
kinetic data with the intraparticle diffusion model demonstrated that arsenite
adsorption onto PS-HFO nanocomposites with larger HFO particles was controlled by
intraparticle diffusion whereas the limitation caused by intraparticle diffusion
was weakened as the particle size of HFO decreased. The adsorption capacity of
the hybrid adsorbents increased with decreased pore size of PS. These results
indicated that the pore structure of the support materials would play a
significant role in the performance of nanoparticle-loaded porous adsorbents.
PMID- 22047723
TI - Synthesis of novel inorganic-organic hybrid materials for simultaneous adsorption
of metal ions and organic molecules in aqueous solution.
AB - In this paper, atom transfer radical polymerization (ATRP) and radical grafting
polymerization were combined to synthesize a novel amphiphilic hybrid material,
meanwhile, the amphiphilic hybrid material was employed in the absorption of
heavy metal and organic pollutants. After the formation of attapulgite (ATP) ATRP
initiator, ATRP block copolymers of styrene (St) and divinylbenzene (DVB) were
grafted from it as ATP-P(S-b-DVB). Then radical polymerization of acrylonitrile
(AN) was carried out with pendent double bonds in the DVD units successfully,
finally we got the inorganic-organic hybrid materials ATP-P(S-b-DVB-g-AN). A
novel amphiphilic hybrid material ATP-P(S-b-DVB-g-AO) (ASDO) was obtained after
transforming acrylonitrile (AN) units into acrylamide oxime (AO) as hydrophilic
segment. The adsorption capacity of ASDO for Pb(II) could achieve 131.6 mg/g, and
the maximum removal capacity of ASDO towards phenol was found to be 18.18 mg/g in
the case of monolayer adsorption at 30 degrees C. The optimum pH was 5 for both
lead and phenol adsorption. The adsorption kinetic suited pseudo-second-order
equation and the equilibrium fitted the Freundlich model very well under optimal
conditions. At the same time FT-IR, TEM and TGA were also used to study its
structure and property.
PMID- 22047724
TI - Role of calcium oxide in sludge granulation and methanogenesis for the treatment
of palm oil mill effluent using UASB reactor.
AB - The granulation process in palm oil mill effluent using calcium oxide-cement kiln
dust (CaO-CKD) provides an attractive and cost effective treatment option. In
this study the efficiency of CaO-CKD at doses of 1.5-20 g/l was tested in batch
experiments and found that 10 g of CaO/l caused the greatest degradation of VFA,
butyrate and acetate. An upflow anaerobic sludge blanket (UASB) reactor was
operated continuously at 35 degrees C for 150 days to investigate the effect of
CaO-CKD on sludge granulation and methanogenesis during start-up. The treatment
of POME emphasized the influence of varying organic loading rates (OLR). Up to
94.9% of COD was removed when the reactor was fed with the 15.5-65.5 g-CODg/l at
an OLR of 4.5-12.5 kg-COD/m(3)d, suggesting the feasibility of using CaO in an
UASB process to treat POME. The ratio of volatile solids/total solids (VS/TS) and
volatile fatty acids in the anaerobic sludge in the UASB reactor decreased
significantly after long-term operation due to the precipitation of calcium
carbonate in the granules. Granulation and methanogenesis decreased with an
increase in the influent CaO-CKD concentration.
PMID- 22047725
TI - Relationship between sports participation and the level of motor coordination in
childhood: a longitudinal approach.
AB - OBJECTIVES: This study examined the stability of motor coordination and the
relationship between motor coordination and organized sports participation over
time. DESIGN: Longitudinal design. METHODS: A total of 371 children between six
and nine years of age at initial testing completed a test battery measuring motor
coordination in three consecutive years and a questionnaire on their club sports
participation in year 1 and year 3 of testing. RESULTS: Correlation coefficients
revealed the motor coordination of children to be a highly stable factor, ranging
from 0.662 (6-8 years) to 0.873 (7-9 years). Results of the Repeated Measures
ANOVA indicated that children who consistently practiced sports in a club
environment over the three years of testing displayed better coordination levels
than children who only partially participated or did not participate in a club
environment at all. Moreover, stability was further indicated as consistent
sports participation over time and changes or lack thereof did not substantially
influence the development of motor coordination over time. In addition, the basic
level of motor coordination and the amount of club sports participation
significantly predicted sports participation two years later. CONCLUSION: The
importance of the stability of motor coordination levels in childhood and its
role in determining organized sports participation may have implications for
talent identification purposes as well as potential health-related benefits in
childhood and throughout the lifespan.
PMID- 22047726
TI - Neural response to eye contact and paroxetine treatment in generalized social
anxiety disorder.
AB - Generalized social anxiety disorder (GSAD) is characterized by excessive fears of
scrutiny and negative evaluation, but neural circuitry related to scrutiny in
GSAD has been little studied. In this study, 16 unmedicated adults with GSAD and
16 matched healthy comparison (HC) participants underwent functional magnetic
resonance imaging to assess neural response to viewed images of faces simulating
movement into eye contact versus away from eye contact. GSAD patients were then
treated for 8 weeks with paroxetine, and 15 patients were re-imaged. At baseline,
GSAD patients had elevated neural response to eye contact in parahippocampal
cortex, inferior parietal lobule, supramarginal gyrus, posterior cingulate and
middle occipital cortex. During paroxetine treatment, symptomatic improvement was
associated with decreased neural response to eye contact in regions including
inferior and middle frontal gyri, anterior cingulate, posterior cingulate,
precuneus and inferior parietal lobule. Both the magnitude of GSAD symptom
reduction with paroxetine treatment and the baseline comparison of GSAD vs. HCs
were associated with neural processing of eye contact in distributed networks
that included regions involved in self-referential processing. These findings
demonstrate that eye contact in GSAD engages neurocircuitry consistent with the
heightened self-conscious emotional states known to characterize GSAD patients
during scrutiny.
PMID- 22047727
TI - Tianeptine reverses stress-induced asymmetrical hippocampal volume and N
acetylaspartate loss in rats: an in vivo study.
AB - Stress-induced hippocampal volume loss and decrease in N-acetylaspartate (NAA)
level have been reported to be associated with impaired neural plasticity and
neuronal damage in adults. Accordingly, reversing structural and metabolite
damage in the hippocampus may be a desirable goal for antidepressant therapy. The
present study investigated the effects of tianeptine on chronic stress-induced
hippocampal volume loss and metabolite alterations in vivo in 24 Sprague-Dawley
rats. Rats were subjected to a consecutive 28-day forced swimming test stress.
Tianeptine (50mg/kg) or saline was administered intragastrically 4h after
swimming each day. Spontaneous behaviors, serum corticosterone concentration,
hippocampal volume and NAA level were evaluated after stress. Chronic tianeptine
treatment counteracted the chronic stress-induced suppression of spontaneous
behaviors, elevated serum corticosterone concentration, reduced hippocampal
volume and decreased NAA level. Moreover, we found asymmetrical right-left
hippocampal volume loss in stressed rats, with the left hippocampus more
sensitive to chronic stress than the right hippocampus. In addition, stressed
rats showed a decreased level of hippocampal metabolites, without significant
loss of hippocampal volume. These findings provide experimental evidence for
impaired structural plasticity of the brain being an important feature of
depressive illness and suggest that prophylactic tianeptine treatments could
reverse structural changes in brain. The structural and neurochemical alterations
in the hippocampus may be valuable indexes for evaluating the prophylactic and
curative effect of antidepressant treatments in depressive and stress-related
disorders.
PMID- 22047729
TI - Detecting abnormalities of corpus callosum connectivity in autism using magnetic
resonance imaging and diffusion tensor tractography.
AB - The corpus callosum (CC) has emerged as one of the primary targets of autism
research. To detect aberrant CC interhemispheric connectivity in autism, we
performed T1-weighted magnetic resonance imaging (MRI) and diffusion tensor
imaging (DTI)-based tractography in 18 children with high functioning autism
(HFA) and 16 well-matched typically developing (TD) children. We compared global
and regional T1 measures (CC volume, and CC density), and the DTI measures
[fractional anisotropy (FA), apparent diffusion coefficient (ADC), average fiber
length (AFL), and fiber number (FN)] of transcallosal fibers, between the two
groups. We also evaluated the relationships between scores on the Childhood
Autism Rating Scale (CARS) and CC T1 or DTI measurements. Significantly less
white matter density in the anterior third of the CC, and higher ADC and lower FN
values of the anterior third transcallosal fiber tracts were found in HFA
patients compared to TD children. These results suggested that the anterior third
CC density and transcallosal fiber connectivity were affected in HFA children.
PMID- 22047728
TI - Cerebellum volume in high-risk offspring from multiplex alcohol dependence
families: association with allelic variation in GABRA2 and BDNF.
AB - Offspring from families with multiple cases of alcohol dependence have a greater
likelihood of developing alcohol dependence (AD) and related substance use
disorders. Greater susceptibility for developing these disorders may be related
to structural differences in brain circuits that influence the salience of
rewards or modify the efficiency of information processing and AD susceptibility.
We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring
from families with multiple cases of alcohol dependence (multiplex families), and
60 low-risk (LR) controls with no family history of alcohol or drug dependence
who were matched for age, gender, socioeconomic status and IQ, with attention
given to possible effects of personal use of substances and maternal use during
pregnancy. Magnetic resonance images were acquired on a General Electric 1.5
Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2
and BDNF variation were tested for their association with cerebellar volumes.
High-risk offspring from multiplex AD families showed greater total volume of the
cerebellum and total gray matter (GM), in comparison with LR controls. An
interaction between allelic variation in GABRA2 and BDNF genes was associated
with GM volumes, suggesting that inherited variation in these genes may promote
early developmental differences in neuronal proliferation of the cerebellum.
PMID- 22047730
TI - Reduced amygdala-orbitofrontal connectivity during moral judgments in youths with
disruptive behavior disorders and psychopathic traits.
AB - We used functional magnetic resonance imaging (fMRI) to investigate dysfunction
in the amygdala and orbitofrontal cortex in adolescents with disruptive behavior
disorders and psychopathic traits during a moral judgment task. Fourteen
adolescents with psychopathic traits and 14 healthy controls were assessed using
fMRI while they categorized illegal and legal behaviors in a moral judgment
implicit association task. fMRI data were then analyzed using random-effects
analysis of variance and functional connectivity. Youths with psychopathic traits
showed reduced amygdala activity when making judgments about legal actions and
reduced functional connectivity between the amygdala and orbitofrontal cortex
during task performance. These results suggest that psychopathic traits are
associated with amygdala and orbitofrontal cortex dysfunction. This dysfunction
may relate to previous findings of disrupted moral judgment in this population.
PMID- 22047732
TI - Analytical metrological characterization of the three-parameter sine fit
algorithm.
AB - The three-parameter sine fit is a well known algorithm used in IEEE standard 1241
2000 for ADC characterization to estimate sine wave parameters from recorded
data. An analytical metrological characterization of that algorithm is carried
out in terms of its design parameters, namely the sampling rate and the number of
samples. Optimal and sub-optimal parameters' sets are found. Focusing on the
amplitude estimation, an approximated statistical characterization of the second
order is given in the most general case of zero mean additive noise, whereas the
exact probability density function is found for the optimal set of algorithm
parameters in the case of additive white Gaussian noise. In this particular case,
the frequency behavior of the algorithm is fully analyzed and the exact frequency
response of the amplitude is also found. An approximated expression that is
easier to use is then presented and discussed. Simulation results for a single
set of parameters are presented in order to graphically illustrate the analytical
results.
PMID- 22047731
TI - Prefrontal hypoactivation during cognitive control in early abstinent
methamphetamine-dependent subjects.
AB - Individuals who abuse methamphetamine (MA) perform at levels below those of
healthy controls on tests that require cognitive control. As cognitive control
deficits may influence the success of treatment for addiction, we sought to help
clarify the neural correlates of this deficit. MA-dependent (n=10, abstinent 4-7
days) and control subjects (n=18) performed a color-word Stroop task, which
requires cognitive control, during functional MRI (fMRI). The task included a
condition in which participants were required to respond to one stimulus
dimension while ignoring another conflicting dimension, and another condition
without conflict. We compared the groups on performance and neural activation in
the two conditions. MA-dependent subjects made more errors and responded more
slowly than controls. Controlling for response times in the incongruent
condition, voxel-wise mixed effects analyses (whole-brain corrected) demonstrated
that MA-dependent subjects had less activation than control subjects in the right
inferior frontal gyrus, supplementary motor cortex/anterior cingulate gyrus and
the anterior insular cortex during the incongruent condition only. MA-dependent
subjects did not exhibit greater activation in any brain region in either of the
Stroop conditions. These preliminary findings suggest that hypofunction in
cortical areas that are important for executive function underlies cognitive
control deficits associated with MA dependence.
PMID- 22047733
TI - Synthesis of near-IR fluorescent oxazine dyes with esterase-labile sulfonate
esters.
AB - Near-IR oxazine dyes are reported that contain sulfonate esters which are rapidly
cleaved by esterase activity to unmask highly polar anionic sulfonates.
Strategies for the synthesis of these dyes included the development of milder dye
condensation conditions with improved functional compatibility and the use of an
alkyl halide that allows for the introduction of esterase-labile sulfonates
without the need for sulfonation of the target molecule.
PMID- 22047735
TI - IL-37: a new anti-inflammatory cytokine of the IL-1 family.
AB - The IL-1 family of cytokines encompasses eleven proteins that each share a
similar beta-barrel structure and bind to Ig-like receptors. Some of the IL-1
like cytokines have been well characterised, and play key roles in the
development and regulation of inflammation. Indeed, IL-1alpha (IL-1F1), IL-1beta
(IL-1F2), and IL-18 (IL-1F4) are well-known inflammatory cytokines active in the
initiation of the inflammatory reaction and in driving Th1 and Th17 inflammatory
responses. In contrast, IL-1 receptor antagonist (IL-1Ra, IL-1F3) and the
receptor antagonist binding to IL-1Rrp2 (IL-36Ra, IL-1F5) reduce inflammation by
blocking the binding of the agonist receptor ligands. In the case of IL-37 (IL
1F7), of which five different splice variants have been described, less is known
of its function, and identification of the components of a heterodimeric receptor
complex remains unclear. Some studies suggest that IL-37 binds to the alpha chain
of the IL-18 receptor in a non-competitive fashion, and this may explain some of
the disparate biological effects that have been reported for mice deficient in
the IL-18R. The biological properties of IL-37 are mainly those of down
regulating inflammation, as assessed in models where human IL-37 is expressed in
mice. In this review, an overview of the role of IL-37 in the regulation of
inflammation is presented. The finding that IL-37 also locates to the nucleus, as
do IL-1alpha and IL-33, for receptor-independent organ/tissue-specific regulation
of inflammation is also reviewed.
PMID- 22047736
TI - [Histological and immunohistochemical profile of sporadic and familial medullary
thyroid carcinoma].
AB - INTRODUCTION: The histological and immunohistochemical profile of medullary
thyroid carcinoma is ill-defined. The objective of this study was to determine
the epidemiological, histological, and immunohistochemical characteristics of
medullary carcinoma and to analyze whether differences exist between sporadic and
familial carcinomas. PATIENTS AND METHODS: Fifty-five histologically confirmed
tumors were studied. Histological slides were reviewed and immunohistochemical
staining of the archival paraffin blocks was performed. RESULTS: Nineteen of the
55 carcinomas (35%) were sporadic, and 36 (65%) familial. Sex distribution was
similar, but familial carcinoma was more common in patients under 40 years of age
(p<0.001). A solid growth pattern and plasmacytoid cells were found in most
cases. C-cell hyperplasia and multicentricity were more frequent findings in
familial carcinoma, while tumor necrosis, hemorrhagic foci, vascular invasion,
and neovascularization were more common in the sporadic type. Immunohistochemical
staining was positive for calcitonin, CEA, bcl-2, and p53 protein. With regard to
staging, familial carcinomas were diagnosed in the earliest stages, when they
were smaller and there were no lymph node metastases (p<0.01). CONCLUSIONS:
Familial cases were more frequent when there was more C-cell hyperplasia and
multicentricity. Sporadic cases more frequently showed foci of necrosis,
hemorrhage, vascular invasion, and neovascularization. Neither histopathological
nor immunohistochemical criteria are useful for differentiating between familial
and sporadic forms.
PMID- 22047737
TI - Local to regional scale industrial heavy metal pollution recorded in sediments of
large freshwater lakes in central Europe (lakes Geneva and Lucerne) over the last
centuries.
AB - This research first focuses on the spatial and temporal patterns of heavy metals
from contrasting environments (highly polluted to deepwater sites) of Lake
Geneva. The mercury (Hg) and lead (Pb) records from two deepwater sites show that
the heavy metal variations before the industrial period are primarily linked to
natural weathering input of trace elements. By opposition, the discharge of
industrial treated wastewaters into Vidy Bay of Lake Geneva during the second
part of the 20th century, involved the sedimentation of highly metal-contaminated
sediments in the area surrounding the WWTP outlet pipe discharge. Eventually, a
new Pb isotope record of sediments from Lake Lucerne identifies the long-term
increasing anthropogenic lead pollution after ca. 1500, probably due to the
development of metallurgical activities during the High Middle Ages. These data
furthermore allows to compare the recent anthropogenic sources of water pollution
from three of the largest freshwater lakes of Western Europe (lakes Geneva,
Lucerne, and Constance). High increases in Pb and Hg highlight the regional
impact of industrial pollution after ca. 1750-1850, and the decrease of metal
pollution in the 1980s due to the effects of remediation strategies such as the
implementation of wastewater treatment plants (WWTPs). However, at all the
studied sites, the recent metal concentrations remain higher than pre-industrial
levels. Moreover, the local scale pollution data reveal two highly contaminated
sites (>100 MUg Pb/g dry weight sediment) by industrial activities, during the
late-19th and early-20th centuries (Lake Lucerne) and during the second part of
the 20th century (Vidy Bay of Lake Geneva). Overall, the regional scale pollution
history inferred from the three large and deep perialpine lakes points out at the
pollution of water systems by heavy metals during the last two centuries due to
the discharge of industrial effluents.
PMID- 22047738
TI - Isotopic signatures for natural versus anthropogenic Pb in high-altitude Mt.
Everest ice cores during the past 800 years.
AB - A long-term record, extending back 800 years (1205 to 2002 AD), of the Pb
isotopic composition ((206)Pb/(207)Pb and (208)Pb/(207)Pb) as well as Pb
concentrations from high altitude Mt. Everest ice cores has the potential to
identify sources and source regions affecting natural and anthropogenic Pb
deposition in central Asia. The results show that the regional natural background
Pb isotope signature (~1.20 for (206)Pb/(207)Pb and ~2.50 for (208)Pb/(207)Pb) in
the central Himalayas was dominated by mineral dust over the last ~750 years from
1205 to 1960s, mostly originating from local sources with occasional
contributions of long-range transported dust probably from Sahara desert and
northwestern India. Since the 1970s, the Pb isotope ratios are characterized by a
continuous decline toward less radiogenic ratios with the least mean ratios of
1.178 for (206)Pb/(207)Pb and 2.471 for (208)Pb/(207)Pb in the period 1990-1996.
The depression of the (206)Pb/(207)Pb and (208)Pb/(207)Pb values during the
corresponding periods is most likely due to an increasing influence of less
radiogenic Pb of anthropogenic origin mainly from leaded gasoline used in South
Asia (India as well as possibly Bangladesh and Nepal). From 1997 to 2002,
isotopic composition tends to show a shift to slightly more radiogenic signature.
This is likely attributed to reducing Pb emissions from leaded gasoline in source
regions, coinciding with the nationwide reduction of Pb in gasoline and
subsequent phase-out of leaded gasoline in South Asia since 1997. An interesting
feature is the relatively high levels of Pb concentrations and enrichment factors
(EF) between 1997 and 2002. Although the reason for this feature remains
uncertain, it would be probably linked with an increasing influence of
anthropogenic Pb emitted from other sources such as fossil fuel combustion and
non-ferrous metal production.
PMID- 22047739
TI - Daily urinary excretion of uranium in members of the public of Southwest Nigeria.
AB - The main aim of this study was to determine and evaluate urinary excretion values
of uranium in members of the public of Southwest Nigeria living in areas of low
environmental uranium. As several uranium mines are running in Nigeria and the
operations could be a risk of contamination for the workers as well as for the
members of the public, biomonitoring of urine could provide information about the
exposure to uranium for the subjects. Therefore, baseline values of uranium in
urine are needed from subjects living in areas without mining activities.
Volunteers of both genders (age range 3 to 78 years) were asked to collect 24h
urine samples. The concentration measurements of uranium in urine were performed
by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In addition, urinary
creatinine values were determined for normalization of the renal uranium relative
to the creatinine concentrations. The urinary uranium concentrations and their
creatinine normalized values ranged from <10.4 to 150 ng L(-1) (median 13.8 ng L(
1)) and from 2.52 to 252.7 ng g(-1) creatinine (median 33.4 ng g(-1) creatinine),
respectively, for adult subjects above 15 years of both genders. An increased
uranium excretion value of 61.6 ng L(-1) (median), and of 76.0 ng g(-1)
creatinine, respectively, were found in young subjects below 15 years. The median
of daily excreted uranium was estimated to be 14.2 ng d(-1) for adults and of
45.1 ng d(-1) for children, respectively. The uranium excretion from males and
females living in Nigeria in a non-mining area was comparable to reference values
reported from other countries with low level of environmental uranium. The data
can be considered as baseline values of urinary uranium in unexposed subjects in
Nigeria.
PMID- 22047740
TI - Informational needs of gynecologic cancer survivors.
AB - OBJECTIVES: In preparation for the launch of a gynecologic oncology survivorship
program, this study looked at the informational needs of women with gynecologic
cancers. Although studies have touched on some of these needs, no published
literature has investigated the comprehensive informational needs of gynecologic
oncology patients within all sites of gynecologic cancers. METHODS: A needs
assessment, consisting of a self-administered questionnaire, was conducted at an
ambulatory gynecologic oncology clinic from August 2010 to March 2011. This study
investigated the informational needs of patients, including the importance of
information, the amount desired, and the preferred mode of delivery.
Informational needs were grouped into six domains: medical, practical, physical,
emotional, social, and spiritual. RESULTS: 185 surveys were analyzed and the
majority of the respondents were Caucasian (77%) and over the age of 50 (66%).
Forty-nine percent of respondents were diagnosed with ovarian cancer, and there
was an even distribution between newly diagnosed patients (38%), those in long
term follow-up (27%), and those with recurrent disease (37%). Overall,
respondents placed more importance on receiving medical information (P<0.01). The
three preferred education modalities were; pamphlets, one-on-one discussions with
health care professionals and websites. Age, education, and disease site were
associated with differing informational needs. CONCLUSIONS: This study has
highlighted the most important informational needs of patients with gynecologic
malignancies in our patient population. This information may guide the
development of clinical survivorship programs and educational resources for
patients in the future.
PMID- 22047741
TI - Physical and chemical effects of ingested plastic debris on short-tailed
shearwaters, Puffinus tenuirostris, in the North Pacific Ocean.
AB - We investigated the plastics ingested by short-tailed shearwaters, Puffinus
tenuirostris, that were accidentally caught during experimental fishing in the
North Pacific Ocean in 2003 and 2005. The mean mass of plastics found in the
stomach was 0.23 g per bird (n=99). Plastic mass did not correlate with body
weight. Total PCB (sum of 24 congeners) concentrations in the abdominal adipose
tissue of 12 birds ranged from 45 to 529 ng/g-lipid. Although total PCBs or
higher-chlorinated congeners, the mass of ingested plastic correlated positively
with concentrations of lower-chlorinated congeners. The effects of toxic
chemicals present in plastic debris on bird physiology should be investigated.
PMID- 22047742
TI - Childhood maltreatment in South Korea: retrospective study.
AB - OBJECTIVE: This study explored the prevalence of childhood maltreatment in South
Korea using the retrospective version of ICAST and the associations between
perceptions of abuse experienced during childhood and recent interpersonal
problems and depression. METHODS: 539 young persons, aged 18-24 years, from
various universities, work places, and clinical settings participated in a study
using the ISPCAN Child Abuse Screening Tool-Retrospective Version (ICAST-R), the
short form of the Korean-Inventory of Interpersonal Problems Circumplex Scale
(KIIP-SC), and the Korean version of the Beck Depression Inventory (K-BDI).
RESULTS: While males reported more physical abuse, females reported being exposed
to more emotional or sexual abuse. The proportion of reported extra-familial or
peer abuse was relatively high. Interpersonal problems and depression were
significantly high for those who experienced all types of abuse during childhood.
Perception of physical abuse as reasonable/justified discipline affected
interpersonal problems and perception of emotional abuse when compared to peers
affected interpersonal problems and depression. Unlike previous studies, this
study identified more depressive symptoms reported with disclosure of sexual
abuse. PRACTICE IMPLICATIONS: These findings highlight the importance of
understanding how one perceives maltreatment. Perceiving an abusive act as a
justifiable disciplinary method may affect reporting as well as longer term
consequences for the victim. A wide range of perpetrators and different settings
in which maltreatment may occur must be considered as influencing these
perceptions. This study contributed to the determination of validity of the ICAST
R for use in wider population surveys.
PMID- 22047743
TI - Adhesion and hemifusion of cytoplasmic myelin lipid membranes are highly
dependent on the lipid composition.
AB - We report the effects of calcium ions on the adhesion and hemifusion mechanisms
of model supported myelin lipid bilayer membranes of differing lipid composition.
As in our previous studies Min et al. [1,2], the lipid compositions used mimic
"healthy" and "diseased-like" (experimental autoimmune encephalomyelitis, EAE)
membranes. Our results show that the interaction forces as a function of membrane
separation distance are well described by a generic model that also (and in
particular) includes the hydrophobic interaction arising from the hydrophobically
exposed (interior) parts of the bilayers. The model is able to capture the
mechanical instability that triggers the onset of the hemifusion event, and
highlights the primary role of the hydrophobic interaction in membrane fusion.
The effects of lipid composition on the fusion mechanism, and the adhesion forces
between myelin lipid bilayers, can be summarized as follows: in calcium-free
buffer, healthy membranes do not present any signs of adhesion or hemifusion,
while diseased membranes hemifuse easily. Addition of 2mM calcium favors adhesion
and hemifusion of the membranes independently of their composition, but the
mechanisms involved in the two processes were different: healthy bilayers
systematically presented stronger adhesion forces and lower energy barriers to
fusion compared to diseased bilayers. These results are of particular relevance
for understanding lesion development (demyelination, swelling, vacuolization
and/or vesiculation) in myelin associated diseases such as multiple sclerosis and
its relationship to lipid domain formation in myelin membranes.
PMID- 22047744
TI - The protective effects of plasma gelsolin on stroke outcome in rats.
AB - BACKGROUND: To date, recombinant tissue plasminogen activator (rtPA) is the only
approved drug for ischemic stroke. It is intravenously administered functioning
as a thrombolytic agent and is used to obtain reperfusion of the affected area of
the brain. Excitotoxicity, inflammation and apoptosis are all involved in delayed
neuronal death following stroke and offer multiple opportunities to intervene
with neuroprotective agents. Gelsolin (GSN) is an actin- and calcium-binding
protein mediating the disassembly of actin filaments and activity of calcium
channels. It also functions as a regulator of apoptosis and inflammatory
responses. This study tests the hypothesis that increasing the concentration of
the form of GSN known as plasma GSN (pGSN) near an infarct will provide
neuroprotection following ischemic stroke. METHODS: We induced middle cerebral
artery occlusion (MCAO) in male rats via intracranial injection of endothelin-1
(ET-1), a potent vasoconstrictor, and then treated with local delivery of pGSN.
Whole brain laser Doppler perfusion imaging was performed through the skull to
assess MCAO effectiveness. Cylinder and vibrissae tests evaluated sensorimotor
function before and 72 h after MCAO. Infarct volumes were examined 72 h after
MCAO via 2, 3, 5-triphenyltetrazolium chloride (TTC) assay. RESULTS: Estimates of
relative cerebral perfusion were significantly decreased in all groups receiving
MCAO with no differences detected between treatments. Despite equivalent initial
strokes, the infarct volume of the pGSN treatment group was significantly reduced
compared with the untreated MCAO rats at 72 h. ET-1 induced significant deficits
in both cylinder and vibrissae tests while pGSN significantly limited these
deficits. CONCLUSION: Gelsolin could be a promising drug for protection against
neurodegeneration following ischemic stroke.
PMID- 22047745
TI - [Ultrasonography for hand surgeons (lecture from the 46th meeting of French
Society of Hand Surgery)].
AB - Ultrasound examination is inexpensive, easily accessible and has numerous
applications. Its diagnostic or even therapeutic use is developing in the context
of hand surgery. The purpose of this work is to review the literature dealing
with hand ultrasonograpy by recalling its physical basis and by showing the
normal and pathological aspects of different structures and pathologies.
PMID- 22047746
TI - The use of N,N'-diallylaldardiamides as cross-linkers in xylan derivatives-based
hydrogels.
AB - N,N'-Diallylaldardiamides (DA) were synthesized from galactaric, xylaric, and
arabinaric acids, and used as cross-linkers together with xylan (X) derivatives
to create new bio-based hydrogels. Birch pulp extracted xylan was derivatized to
different degrees of substitution of 1-allyloxy-2-hydroxy-propyl (A) groups
combined with 1-butyloxy-2-hydroxy-propyl (B) and/or hydroxypropyl (HP) groups.
The hydrogels were prepared in water solution by UV induced free-radical cross
linking polymerization of derivatized xylan polymers without DA cross-linker
(xylan derivative hydrogel) or in the presence of 1 or 5 wt% of DA cross-linker
(DA hydrogel). Commercially available cross-linker (+)-N,N'-diallyltartardiamide
(DAT) was also used. The degree of substitution (DS) of A, B, and HP groups in
xylan derivatives was analyzed according to (1)H NMR spectra. The DS values for
the cross-linkable A groups of the derivatized xylans were 0.4 (HPX-A), 0.2 (HPX
BA), and 0.4 (X-BA). The hydrogels were examined with FT-IR and elemental
analysis which proved the cross-linking successful. Water absorption of the
hydrogels was examined in deionized water. Swelling degrees up to 350% were
observed. The swollen morphology of the hydrogels was assessed by scanning
electron microscopy (SEM). The presence of cross-linkers in DA hydrogels had only
a small impact on the water absorbency when compared to xylan derivative
hydrogels but a more uniform pore structure was achieved.
PMID- 22047747
TI - Synthesis of water-soluble multidentate aminoalcohol beta-cyclodextrin
derivatives via epoxide opening.
AB - New highly soluble beta-aminoalcohol beta-cyclodextrin (beta-CD) derivatives have
been synthesized via nucleophilic epoxide opening reactions with mono-6-amino
mono-6-deoxy-permethyl-beta-CD and mono-6-amino mono-6-deoxy-beta-CD. The binding
properties of the beta-CD were enhanced by linking aminoalcohol subunits which
caused its solubility to improve markedly. The reaction conditions were optimised
using microwave irradiation giving moderate-to-good yields with a series of
epoxides. A regioselective epoxide opening reaction was observed in the reaction
with styrene oxide while the stereoselectivity was strictly dependent on
substrate structure.
PMID- 22047748
TI - Mice spermatogonial stem cells transplantation induces macrophage migration into
the seminiferous epithelium and lipid body formation: high-resolution light
microscopy and ultrastructural studies.
AB - Transplantation of spermatogonial stem cells (SSCs), the male germline stem
cells, in experimental animal models has been successfully used to study
mechanisms involved in SSC self-renewal and to restore fertility. However, there
are still many challenges associated with understanding the recipient immune
response for SSCs use in clinical therapies. Here, we have undertaken a detailed
structural study of macrophages elicited by SSCs transplantation in mice using
both high-resolution light microscopy (HRLM) and transmission electron microscopy
(TEM). We demonstrate that SSCs transplantation elicits a rapid and potent
recruitment of macrophages into the seminiferous epithelium (SE). Infiltrating
macrophages were derived from differentiation of peritubular monocyte-like cells
into typical activated macrophages, which actively migrate through the SE,
accumulate in the tubule lumen, and direct phagocytosis of differentiating germ
cells and spermatozoa. Quantitative TEM analyses revealed increased formation of
lipid bodies (LBs), organelles recognized as intracellular platforms for
synthesis of inflammatory mediators and key markers of macrophage activation,
within both infiltrating macrophages and Sertoli cells. LBs significantly
increased in number and size in parallel to the augmented macrophage migration
during different times post-transplantation. Our findings suggest that LBs may be
involved with immunomodulatory mechanisms regulating the seminiferous tubule
niche after SSC transplantation.
PMID- 22047749
TI - Fingermark detection on non-porous and semi-porous surfaces using YVO4:Er,Yb
luminescent upconverting particles.
AB - This article describes the use of an anti-Stokes luminescent material
(upconverter), yttrium vanadate doped with ytterbium and erbium (YVO(4):Er,Yb),
for the development of latent fingermarks on a range of non-porous surfaces. Anti
Stokes luminescent materials emit light at shorter wavelengths than the
excitation wavelength. This property is unusual in both natural and artificial
materials commonly found as exhibits in forensic science casework. As a result,
fingermark detection techniques based on anti-Stokes luminescence are potentially
extremely sensitive and selective. Latent fingermarks on non-luminescent and
inherently luminescent substrates, including Australian polymer banknotes (a well
known 'difficult' surface), were developed with YVO(4):Er,Yb by dry powder and
wet powder techniques. The effectiveness of YVO(4):Er,Yb for fingermark detection
was compared with that of cyanoacrylate fuming and of sodium yttrium
tetrafluoride doped with ytterbium and erbium (NaYF(4):Er,Yb). The results
illustrate some benefit of luminescent up-converting phosphors over traditional
luminescence techniques for the detection of latent fingermarks.
PMID- 22047750
TI - Anabolic androgenic steroids abuse and cardiac death in athletes: morphological
and toxicological findings in four fatal cases.
AB - Anabolic androgenic steroids (AAS) are the main class of doping agents and their
consumption produces adverse effects involving several organs and systems. Three
cases of sudden cardiac death (SCD) and one of death due to congestive heart
failure of previously healthy athletes who were AAS users are herein reported.
Concentric cardiac hypertrophy with focal fibrosis (one case), dilated
cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis
(one case) were observed and most probably relate to the final event. Molecular
investigation for viral genomes was positive in one case (Ebstein virus). Our
data confirm previous findings, showing that the most typical cardiac abnormality
in AAS abusers is left ventricular hypertrophy, associated with fibrosis and
myocytolysis. An exceptional cardiovascular substrate was represented by the case
with drug induced eosinophilic myocarditis. These features are at risk of
ventricular arrhythmias as well as congestive heart failure. The cause-effect
relationship between AAS abuse and cardiac death can be established only by a
rigorous methodology with the use of standardized protocols, including precise
morphological studies of all target organs to search for chronic toxic effects.
Laboratory investigations should focus on AAS searching on a wide range of
biological matrices to demonstrate type, magnitude and time of exposure.
PMID- 22047751
TI - Screening of gunshot residues using desorption electrospray ionisation-mass
spectrometry (DESI-MS).
AB - Several studies have indicated that there are potential environmental sources of
particles resembling inorganic primer found in gunshot residues (GSR); as a
consequence examiners are reluctant to unambiguously assign the origin of
inorganic particles. If organic gunshot residues (OGSR) were found in combination
with inorganic particles, the possibility of environmental sources could be
potentially eliminated, thereby significantly enhancing the strength of the
evidence. Methods have been previously described whereby GSR specimens can be
analysed for the presence of OGSR or inorganic GRS (IGSR). However, no methods
have been reported that allow the analysis of both OGSR and IGSR on the same
specimen. Described in this article is a direct method using desorption
electrospray ionisation-mass spectrometry (DESI-MS) for the detection of methyl
centralite (MC), ethyl centralite (EC) and diphenylamine (DPA) on adhesive tape
GSR stubs typically used for scanning electron microscopy-energy-dispersive X-ray
(SEM-EDX) analysis. The optimisation of numerous parameters was conducted using
an experimental design. The results indicate that direct analysis of these
organic components of GSR is possible although some limitations were also
identified. This initial investigation has also indicated that subjecting stubs
to DESI analysis does not interfere with subsequent SEM-EDX analysis of primer
residues; therefore the technique described herein allows a comprehensive
examination of GSR that would be highly probative in the event that both OGSR and
IGSR are detected in the same specimen.
PMID- 22047752
TI - Simultaneous detection of seventeen drugs of abuse and metabolites in hair using
solid phase micro extraction (SPME) with GC/MS.
AB - INTRODUCTION: The analysis of pediatric and adult hair is a useful non-invasive
biomarker to effectively detect long term exposure to various xenobiotics,
specifically drugs of abuse such as cocaine, opiates and amphetamines. Very often
individuals are using, or are exposed to multiple drugs simultaneously and
therefore it is important to be able to detect them in the same analysis. We have
developed a sensitive and specific solid phase micro extraction (SPME) coupled
with gas chromatography mass spectrometry (GC/MS) to detect 17 different analytes
in hair using a single extraction method. METHOD: Five milligrams of hair is
extracted overnight, subjected to solid phase extraction (SPE) and then to SPME
GC/MS. The aimed analytes include amphetamine, methamphetamine, MDA, MDMA,
cocaine, benzoylecognine, norcocaine, cocaethylene, methadone, codeine, morphine,
6-AM, oxycodone, oxymorphone, hydrocodone, hydromorphone and meperidone. RESULTS:
The following are the LOD of the various drugs: 0.2ng/mg hair for amphetamine,
methamphetamine, MDA, MDMA, morphine, codeine, 6-AM, oxycodone, oxymorphone,
hydromorphone, hydrocodone, meperidine and 0.13ng/mg hair for cocaine,
benzoylecognine, cocaethylene, norcocaine and methadone. CONCLUSION: This GC/MS
method is sensitive and specific to detect the presence of these 17 analytes in
as little as 5mg of hair and is especially useful for newborn and child hair
analysis where the amount of hair is often very limited.
PMID- 22047753
TI - Short term outcomes after cardiac surgery in a Jehovah's Witness population: an
institutional experience.
AB - BACKGROUND: Minimising blood transfusion has a number of medical and logistical
benefits, and is of particular importance for followers of the Jehovah's Witness
faith. We examined the short term outcomes in this group of patients based on our
institutional practice over the past decade. PATIENTS/METHODS: Data on 59
patients (73% male, mean age 66 years [range 40-83]) who identified as Jehovah's
Witness was prospectively collected and retrospectively analysed from a
systematised database over the period from January 1999 to June 2010. Mean
logistic Euroscore was 4.5, with coronary artery bypass procedures most common
(44/59, 75%) followed by aortic valve replacement (6/59, 10%). RESULTS: Average
haemoglobin (Hb) fell from 142 g/L preoperatively to 109 g/L at discharge. Output
from cardiac drains was reduced in patients who received aprotinin (34/59, 58%,
p=0.05) compared to tranexaemic acid (11/59, 18%) or no antifibrinolytic (15/59,
25%). Operative mortality was 1/59 (1.7%) with an average length of postoperative
stay of 6.2 days. Morbidity rates for neurologic deficit 2/59 (3.4%), deep
sternal infection 1/59 (1.7%) and postoperative myocardial infarction 1/59 (1.7%)
were within accepted ranges. CONCLUSION: Cardiac surgery can be performed safely
in Jehovah's Witness patients with acceptable outcomes.
PMID- 22047754
TI - Reverse contrast and substructures in protein micro-patterns on 3D polymer
surfaces.
AB - We characterize an approach enabling protein patterning over broad polymer areas
based on selective protein adsorption on surfaces of spin-cast amino-terminated
polystyrene structured topographically with elastomer molds (capillary force
lithography) and passivated locally against adsorption with poly(ethylene oxide)
silanes printed with flat elastomer stamps (inverted micro-contact printing).
Atomic force microscopy reveals uniformity of PS-NH(2) films with stripes of
grooves and elevations alternating with periodicity 4